HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

This page is under construction

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Adult T-cell Leukemia/Lymphoma.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Prasad R. Kopparapu, PhD and Ferrin C. Wheeler, PhD, FACMG

Vanderbilt University Medical Center

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	T-cell and NK-cell lymphoid proliferations and lymphomas
Family	Mature T-cell and NK-cell neoplasms
Type	Mature T-cell and NK-cell leukaemias
Subtype(s)	Adult T-cell leukaemia/lymphoma

Related Terminology


Acceptable	Adult T-cell leukaemia/lymphoma, HTLV-1 associated
Not Recommended	N/A

Gene Rearrangements

Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Driver Gene	Fusion(s) and Common Partner Genes	Molecular Pathogenesis	Typical Chromosomal Alteration(s)	Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: ABL1	EXAMPLE: BCR::ABL1	EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.	EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: Common (CML)	EXAMPLE: D, P, T	EXAMPLE: Yes (WHO, NCCN)	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
EXAMPLE: CIC	EXAMPLE: CIC::DUX4	EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5.	EXAMPLE: t(4;19)(q25;q13)	EXAMPLE: Common (CIC-rearranged sarcoma)	EXAMPLE: D		EXAMPLE: DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
EXAMPLE: ALK	EXAMPLE: ELM4::ALK Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1	EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18.	EXAMPLE: N/A	EXAMPLE: Rare (Lung adenocarcinoma)	EXAMPLE: T		EXAMPLE: Both balanced and unbalanced forms are observed by FISH (add references).
EXAMPLE: ABL1	EXAMPLE: N/A	EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.	EXAMPLE: N/A	EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)	EXAMPLE: D, P, T

editv4:Chromosomal Rearrangements (Gene Fusions)

The content below was from the old template. Please incorporate above.

Tandem duplications of 2q33.2 segments cause formation of CTLA4-CD28 and ICOS-CD28 fusion products that render prolonged co-stimulatory signals^[1].

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
2q33.2 (Tandem Duplication)	5’ CTLA/3’CD28	der(2)	7%
2q33.2 (Tandem Duplication)	5’ICOS/3’CD28	der(2)	7%

End of V4 Section

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:
Chromosomal Rearrangements (Gene Fusions)

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal Patterns

Gene Mutations (SNV/INDEL)

ATLL diagnosis can be made based on seropositivity for HTLV-1 and histologically and/or cytologically proven peripheral T cell lymphoma (PTCL). Diagnosis can also be made by quantifying proviral DNA loads (PVLs) in peripheral blood mononuclear cells using real time PCR. PVL of an infected person can range from 0.01 to 50% or higher. Other diagnostic criteria includes appropriate patient demographic information, hypercalcemia, skin lesions and a leukemic phase.

The prognosis of ATLL is largely dependent on the subtype. The acute and lymphomatous subtypes are aggressive, with a median survival of 6.2 months and 10.2 months, respectively. The less-aggressive chronic and smoldering subtypes have a median survival of approximately 4.5 years^[2]. Prognostic factors include clinical variant, age, serum calcium and LDH levels as well as detection of opportunistic infections of parasitic or viral types and p16 gene deletion and p53 mutation.

As ATLL is resistant to most chemotherapy, there is no standard chemotherapy regimen. High dose combination chemotherapy and bone marrow transplantation have been tried previously^[3]. Monoclonal antibody-based therapies against IL-2R (anti-Tac), CCR4 (mogamulizumab) and CD52 (alemtuzumab) have also been attempted along with arsenic trioxide, interferon α and zidovudine^[4].

End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

Chr #	Gain, Loss, Amp, LOH	Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]	Relevant Gene(s)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7	EXAMPLE: Unknown	EXAMPLE: D, P	EXAMPLE: No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8	EXAMPLE: Unknown	EXAMPLE: D, P		EXAMPLE: Common recurrent secondary finding for t(8;21) (add references).
EXAMPLE: 17	EXAMPLE: Amp	EXAMPLE: 17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]	EXAMPLE: ERBB2	EXAMPLE: D, P, T		EXAMPLE: Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

editv4:Genomic Gain/Loss/LOH

The content below was from the old template. Please incorporate above.

ATLL with high number of chromosomal imbalances is associated with poor survival^[5]^[6]^[7]^[8].

Chromosome Number	Gain/Loss/Amp/LOH	Region
1	Gain	1q
2	Gain	2p
3	Gain	3p
4	Gain	4q
6	Loss	6q
7	Gain	7p, 7q
9	Amp	9p
10	Loss	10p
13	Loss	13q
14	Gain	14q
16	Loss	16q
18	Loss	18p

End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern	Molecular Pathogenesis	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
EXAMPLE: Co-deletion of 1p and 18q	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).	EXAMPLE: Common (Oligodendroglioma)	EXAMPLE: D, P
EXAMPLE: Microsatellite instability - hypermutated		EXAMPLE: Common (Endometrial carcinoma)	EXAMPLE: P, T

editv4:Characteristic Chromosomal Aberrations / Patterns

The content below was from the old template. Please incorporate above.

Cytogenetic studies show that ATLL often has a complex abnormal karyotype without a single distinct abnormality. Observed recurrent abnormalities include trisomy for 3, 7 or 21 and monosomy for X as well as deletion of Y and abnormalities of chromosome 6 and 14. Chromosome 14 rearrangements involving TCRA and TCRD at 14q11 and TCL1 at 14q32 have been documented^[9]. Frequent deletions in known fragile sites have been detected in over 500 patients^[1].

End of V4 Section

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Gene	Genetic Alteration	Tumor Suppressor Gene, Oncogene, Other	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE:EGFR	EXAMPLE: Exon 18-21 activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (lung cancer)	EXAMPLE: T	EXAMPLE: Yes (NCCN)	EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations	EXAMPLE: Variable LOF mutations	EXAMPLE: Tumor Supressor Gene	EXAMPLE: Common (breast cancer)	EXAMPLE: P		EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations	EXAMPLE: Activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (melanoma)	EXAMPLE: T

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

The content below was from the old template. Please incorporate above.

Over 10% of ATLL cases harbor mostly gain of function mutations. ATLL harbors multiple recurrent mutations in genes involved in the TCR-NF-κB pathway, tumor suppressors, transcription factors involved in cell growth and proliferation, apoptosis, and immune surveillance^[10]^[8]^[11].

Gene	Oncogene/Tumor Suppressor/Other	Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)
PLCG1	TCR – NF-κB Signaling	GOF
PKCB	TCR – NF-κB Signaling	GOF
CARD11	TCR – NF-κB Signaling	GOF
VAV1	TCR – NF-κB Signaling	GOF
CD237	TCR – NF-κB Signaling	GOF
RHOA	RAS-RAF-ERK pathway	GOF
IRF4	Transcription Factor	GOF
NOTCH1	Transcription Factor	GOF
FBXW7	Transcription Factor	GOF
STAT3	Transcription Factor	GOF
TNFAIP3/A20	TCR – NF-κB Signaling	LOF
NFKBIA/IκBα	TCR – NF-κB Signaling	LOF
TRAF3	TCR – NF-κB Signaling	LOF
CBLB	TCR – NF-κB Signaling	LOF
TP53	Tumor Suppressor	LOF
CDKN2	Tumor Suppressor	LOF
GATA3	Transcription Factor	LOF
EP300	Transcription Factor	LOF
FAS	Apoptosis	LOF
WWOX	Apoptosis	LOF
HLA-B	Immune Surveillance	LOF
B2M	Immune Surveillance	LOF
PD-L1	Immune Surveillance	Amplification

Other Mutations

Type	Gene/Region/Other
Concomitant Mutations	EXAMPLE: IDH1 R123H
Secondary Mutations	EXAMPLE: Trisomy 7
Mutually Exclusive	EXAMPLE: EGFR Amplification

End of V4 Section

Epigenomic Alterations

Epigenetic alterations also result in dysregulated TCR/NF-κB signaling in ATLL. DNA hypermethylation of CpG islands is detected in 1/3^rd of all ATLL patients. As a result, genes involved in Cys2-His2 (C2H2) zinc finger genes and those encoding MHC class I molecules are silenced^[1].

ATLL patients have high expression of polycomb repressive complex (PRC) 2 components like EZH2, its homolog EZH1 and H3K27 methylase causing accumulation of trimethylation of H3K27 and altering the expression of over half of the genes. The severity of the disease is linked to continued down regulation of genes^[12].

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations	EXAMPLE: Histone modification, chromatin remodeling	EXAMPLE: Abnormal gene expression program

editv4:Genes and Main Pathways Involved

The content below was from the old template. Please incorporate above.

The most important genes involved in the development and progress of ATLL are the Tax and HBZ contributed by the HTLV-1 virus and genes listed in gene mutations table (above) from the host. The main pathways involved are TCR-NF-κB signaling by gain of function and amplifications in PLCG1, VAV1 and FYN, CD28, PRKCB, CARD11, IRF4 and RHOA; and loss of function mutations or deletions in CBLB, TRAF, TNFAIP3 and CSNK1A1^[1].

Genes involving the immune surveillance program are also heavy altered to evade the immune response either by deletions in MHC class1 molecules, CD58, FAS or constitutive activation of PD-L1.

Genes involved in the Lymphocyte activation and differentiation(IRF4, GATA3, IKZF2) are also altered.

Chemokine receptors including CCR4 and CCR7 are responsible for the infiltration of neoplastic cells into other organs along with activation of PI3K/AKT signaling.

The epigenetic mechanism is also exploited to alter gene expression and promote ATLL progression as explained above.

End of V4 Section

Genetic Diagnostic Testing Methods

Initial diagnosis of ATLL should include a comprehensive physical exam with skin evaluation and CT scans of the chest, abdomen and pelvis. The laboratory evaluation should include: a complete blood count (CBC), metabolic panel (serum electrolyte levels, calcium, creatinine and blood urea nitrogen) and serum LDH levels. Testing methods including PCR, Flow Cytometry, ELISA, serology, and immunohistochemistry in addition to morphologic studies may be employed to diagnose ATLL^[13].

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

Put a link here or anywhere appropriate in this page (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)

↑ ^1.0 ^1.1 ^1.2 ^1.3 Kataoka, Keisuke; et al. (2015-11). "Integrated molecular analysis of adult T cell leukemia/lymphoma". Nature Genetics. 47 (11): 1304–1315. doi:10.1038/ng.3415. ISSN 1546-1718. PMID 26437031. Check date values in: |date= (help)
↑ Shimoyama, M. (1991-11). "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)". British Journal of Haematology. 79 (3): 428–437. doi:10.1111/j.1365-2141.1991.tb08051.x. ISSN 0007-1048. PMID 1751370. Check date values in: |date= (help)
↑ Hishizawa, Masakatsu; et al. (2010-08-26). "Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study". Blood. 116 (8): 1369–1376. doi:10.1182/blood-2009-10-247510. ISSN 1528-0020. PMID 20479287.
↑ Hermine, Olivier; et al. (02 2018). "A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies". Advances in Therapy. 35 (2): 135–152. doi:10.1007/s12325-018-0658-4. ISSN 1865-8652. PMC 5818559. PMID 29411267. Check date values in: |date= (help)
↑ Itoyama, T.; et al. (2001-06-01). "Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki". Blood. 97 (11): 3612–3620. doi:10.1182/blood.v97.11.3612. ISSN 0006-4971. PMID 11369658.
↑ Tsukasaki, K.; et al. (2001-06-15). "Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course". Blood. 97 (12): 3875–3881. doi:10.1182/blood.v97.12.3875. ISSN 0006-4971. PMID 11389029.
↑ Oshiro, Aya; et al. (2006-06-01). "Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma". Blood. 107 (11): 4500–4507. doi:10.1182/blood-2005-09-3801. ISSN 0006-4971. PMID 16484591.
↑ ^8.0 ^8.1 Kataoka, Keisuke; et al. (01 11, 2018). "Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma". Blood. 131 (2): 215–225. doi:10.1182/blood-2017-01-761874. ISSN 1528-0020. PMC 5757690. PMID 29084771. Check date values in: |date= (help)
↑ "Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma". Blood. 70 (5): 1554–1564. 1987-11. ISSN 0006-4971. PMID 2889485. Check date values in: |date= (help)
↑ Kogure, Yasunori; et al. (2017-09). "Genetic alterations in adult T-cell leukemia/lymphoma". Cancer Science. 108 (9): 1719–1725. doi:10.1111/cas.13303. ISSN 1349-7006. PMC 5581529. PMID 28627735. Check date values in: |date= (help)
↑ Kataoka, Keisuke; et al. (2015-11). "Integrated molecular analysis of adult T cell leukemia/lymphoma". Nature Genetics. 47 (11): 1304–1315. doi:10.1038/ng.3415. ISSN 1546-1718. PMID 26437031. Check date values in: |date= (help)
↑ Fujikawa, Dai; et al. (2016-04-07). "Polycomb-dependent epigenetic landscape in adult T-cell leukemia". Blood. 127 (14): 1790–1802. doi:10.1182/blood-2015-08-662593. ISSN 1528-0020. PMID 26773042.
↑ NCCN Clinical Practice Guidelines in Oncology, T-Cell Lymphomas, Version 1.2021. Available at NCCN.org.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):

*Citation of this Page: “Adult T-cell leukaemia/lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 07/3/2025, https://ccga.io/index.php/HAEM5:Adult_T-cell_leukaemia/lymphoma.

[:1-1] 1.0 ^1.1 ^1.2 ^1.3 Kataoka, Keisuke; et al. (2015-11). "Integrated molecular analysis of adult T cell leukemia/lymphoma". Nature Genetics. 47 (11): 1304–1315. doi:10.1038/ng.3415. ISSN 1546-1718. PMID 26437031. Check date values in: |date= (help)

[:3-2] Shimoyama, M. (1991-11). "Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)". British Journal of Haematology. 79 (3): 428–437. doi:10.1111/j.1365-2141.1991.tb08051.x. ISSN 0007-1048. PMID 1751370. Check date values in: |date= (help)

[3] Hishizawa, Masakatsu; et al. (2010-08-26). "Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study". Blood. 116 (8): 1369–1376. doi:10.1182/blood-2009-10-247510. ISSN 1528-0020. PMID 20479287.

[4] Hermine, Olivier; et al. (02 2018). "A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies". Advances in Therapy. 35 (2): 135–152. doi:10.1007/s12325-018-0658-4. ISSN 1865-8652. PMC 5818559. PMID 29411267. Check date values in: |date= (help)

[5] Itoyama, T.; et al. (2001-06-01). "Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki". Blood. 97 (11): 3612–3620. doi:10.1182/blood.v97.11.3612. ISSN 0006-4971. PMID 11369658.

[6] Tsukasaki, K.; et al. (2001-06-15). "Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course". Blood. 97 (12): 3875–3881. doi:10.1182/blood.v97.12.3875. ISSN 0006-4971. PMID 11389029.

[7] Oshiro, Aya; et al. (2006-06-01). "Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma". Blood. 107 (11): 4500–4507. doi:10.1182/blood-2005-09-3801. ISSN 0006-4971. PMID 16484591.

[:2-8] 8.0 ^8.1 Kataoka, Keisuke; et al. (01 11, 2018). "Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma". Blood. 131 (2): 215–225. doi:10.1182/blood-2017-01-761874. ISSN 1528-0020. PMC 5757690. PMID 29084771. Check date values in: |date= (help)

[9] "Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma". Blood. 70 (5): 1554–1564. 1987-11. ISSN 0006-4971. PMID 2889485. Check date values in: |date= (help)

[10] Kogure, Yasunori; et al. (2017-09). "Genetic alterations in adult T-cell leukemia/lymphoma". Cancer Science. 108 (9): 1719–1725. doi:10.1111/cas.13303. ISSN 1349-7006. PMC 5581529. PMID 28627735. Check date values in: |date= (help)

[11] Kataoka, Keisuke; et al. (2015-11). "Integrated molecular analysis of adult T cell leukemia/lymphoma". Nature Genetics. 47 (11): 1304–1315. doi:10.1038/ng.3415. ISSN 1546-1718. PMID 26437031. Check date values in: |date= (help)

[12] Fujikawa, Dai; et al. (2016-04-07). "Polycomb-dependent epigenetic landscape in adult T-cell leukemia". Blood. 127 (14): 1790–1802. doi:10.1182/blood-2015-08-662593. ISSN 1528-0020. PMID 26773042.

[:4-13] NCCN Clinical Practice Guidelines in Oncology, T-Cell Lymphomas, Version 1.2021. Available at NCCN.org.

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HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

Latest revision as of 12:09, 3 July 2025

Contents

Primary Author(s)*

WHO Classification of Disease

Related Terminology

Gene Rearrangements

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal or Other Global Mutational Patterns

Gene Mutations (SNV/INDEL)

Other Mutations

Epigenomic Alterations

Genes and Main Pathways Involved

Genetic Diagnostic Testing Methods

Familial Forms

Additional Information

Links

References

Notes

Navigation menu

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 {{DISPLAYTITLE:Adult T-cell leukaemia/lymphoma}}
-[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
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-<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Adult T-cell Leukemia/Lymphoma]].
+<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Adult T-cell Leukemia/Lymphoma]].
 }}</blockquote>
+<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>
 ==Primary Author(s)*==
@@ Line 11: / Line 14: @@
 Vanderbilt University Medical Center
+==WHO Classification of Disease==
-__TOC__
+{| class="wikitable"
+!Structure
-==Cancer Category / Type==
+!Disease
+|-
-Mature T- and NK-Cell Neoplasms
+|Book
+|Haematolymphoid Tumours (5th ed.)
-==Cancer Sub-Classification / Subtype==
+|-
+|Category
-Adult T-Cell Leukemia/lymphoma (ATLL)
+|T-cell and NK-cell lymphoid proliferations and lymphomas
+|-
-==Definition / Description of Disease==
+|Family
+|Mature T-cell and NK-cell neoplasms
-Adult T-cell Leukemia/Lymphoma (ATLL) is a systemic, aggressive T-cell malignancy cause by chronic infection of human T lymphotropic virus 1 (HTLV-1) with poor prognosis<ref>Thiele, J. et al., (2017). Adult T-cell leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p363-367</ref>.
+|-
+|Type
-==Synonyms / Terminology==
+|Mature T-cell and NK-cell leukaemias
+|-
-Adult T-cell leukemia, Adult T-cell lymphoma, HTLV-1 associated adult T-cell leukemia-lymphoma.
+|Subtype(s)
+|Adult T-cell leukaemia/lymphoma
-==Epidemiology / Prevalence==
+|}
-ATLL is endemic in many parts of Southwestern Japan, the Caribbean basin, Sub-Saharan Africa, South America, Romania, Northern Iran, parts of the Middle East and Australo-Melanesia<ref name=":0">{{Cite journal|last=Gessain|first=Antoine|last2=Cassar|first2=Olivier|date=2012|title=Epidemiological Aspects and World Distribution of HTLV-1 Infection|url=https://pubmed.ncbi.nlm.nih.gov/23162541|journal=Frontiers in Microbiology|volume=3|pages=388|doi=10.3389/fmicb.2012.00388|issn=1664-302X|pmc=3498738|pmid=23162541}}</ref><ref>{{Cite journal|last=Mehta-Shah|first=Neha|last2=Ratner|first2=Lee|last3=Horwitz|first3=Steven M.|date=08 2017|title=Adult T-Cell Leukemia/Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28796966|journal=Journal of Oncology Practice|volume=13|issue=8|pages=487–492|doi=10.1200/JOP.2017.021907|issn=1935-469X|pmc=6366298|pmid=28796966}}</ref>.
-ATLL occurs only in adults between 30 to 90 years of age with an average age of 58 years. The male-to-female ratio is 1.5:1<ref>{{Cite journal|last=Rocquain|first=Julien|last2=Carbuccia|first2=Nadine|last3=Trouplin|first3=Virginie|last4=Raynaud|first4=Stéphane|last5=Murati|first5=Anne|last6=Nezri|first6=Meyer|last7=Tadrist|first7=Zoulika|last8=Olschwang|first8=Sylviane|last9=Vey|first9=Norbert|date=2010-08-02|title=Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias|url=https://pubmed.ncbi.nlm.nih.gov/20678218|journal=BMC cancer|volume=10|pages=401|doi=10.1186/1471-2407-10-401|issn=1471-2407|pmc=2923633|pmid=20678218}}</ref>.
-Transmission occurs through breast milk, sexual fluids, peripheral blood and blood products<ref name=":0" />.
-==Clinical Features==
+==Related Terminology==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 {| class="wikitable"
-|'''Signs and Symptoms'''
+|+
-|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+|Acceptable
+|Adult T-cell leukaemia/lymphoma, HTLV-1 associated
-EXAMPLE B-symptoms (weight loss, fever, night sweats)
-EXAMPLE Fatigue
-EXAMPLE Lymphadenopathy (uncommon)
 |-
-|'''Laboratory Findings'''
+|Not Recommended
-|EXAMPLE Cytopenias
+|N/A
-EXAMPLE Lymphocytosis (low level)
 |}
+==Gene Rearrangements==
-<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
-ATLL is classified into four clinical subtypes: Acute, Lymphoma, Chronic and Smoldering<ref name=":3">{{Cite journal|last=Shimoyama|first=M.|date=1991-11|title=Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)|url=https://pubmed.ncbi.nlm.nih.gov/1751370|journal=British Journal of Haematology|volume=79|issue=3|pages=428–437|doi=10.1111/j.1365-2141.1991.tb08051.x|issn=0007-1048|pmid=1751370}}</ref>.
-<u>Acute</u>: Most common type (65% of patients) with elevated WBC count, skin rash and generalized lymphadenopathy, hypercalcemia, hepatosplenomegaly, elevated LDH and frequent opportunistic infections like pneumocystis jirovecii pneumonia and strongyloidiasis.
-<u>Lymphoma</u>: The lymphomatous variant is characterized by lymphadenopathy, absence of lymphocytosis, possible extranodal lesions with minimal peripheral blood involvement and less frequent hypercalcemia.
-<u>Chronic</u>: The chronic variant can progress to acute or lymphomatous subtype. This variant manifests with lymphocytosis and exfoliative skin lesions.  Atypical lymphocytes are fewer in number in peripheral blood. There can be mild hepatosplenomegaly and lymphadenopathy. Hypercalcemia is not observed, and no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion.
-<u>Smoldering</u>: This variant may also progress to the acute subtype upon long duration. This variant may present with skin or lung lesions. More than 5% circulating abnormal T-cell lymphocytes can be found in the absence of leukocytosis. No manifestation of hypercalcemia, hepatosplenomegaly or lymphadenopathy.
-</blockquote>
-==Sites of Involvement==
-In addition to lymph node involvement, there is involvement in extranodal sites like spleen, skin, lung, liver, gastrointestinal tract and CNS, making this a systemic disease with peripheral blood involvement<ref>{{Cite journal|last=Bunn|first=P. A.|last2=Schechter|first2=G. P.|last3=Jaffe|first3=E.|last4=Blayney|first4=D.|last5=Young|first5=R. C.|last6=Matthews|first6=M. J.|last7=Blattner|first7=W.|last8=Broder|first8=S.|last9=Robert-Guroff|first9=M.|date=1983-08-04|title=Clinical course of retrovirus-associated adult T-cell lymphoma in the United States|url=https://pubmed.ncbi.nlm.nih.gov/6602943|journal=The New England Journal of Medicine|volume=309|issue=5|pages=257–264|doi=10.1056/NEJM198308043090501|issn=0028-4793|pmid=6602943}}</ref>.
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
-==Morphologic Features==
-The morphological features of ATLL in skin include erythema, papules, and nodules based on macroscopic examination and perivascular infiltration of atypical lymphoid cells, diffuse infiltration of medium to large sized atypical lymphoid cells and infiltration of large atypical lymphoid cell as per histopathological observations.
-Lymph node lesions present as pleomorphic small, medium and large cell types, anaplastic and an angioimmunoblastic T-cell lymphoma type.
-Infiltration of atypical lymphoid cells with irregular or round nuclei is seen in the bone marrow cavity with detection of hypercalcemia.
-In liver, infiltration of atypical medium to large sized lymphoid cells with irregular nuclei is seen.
-Diffuse, pleomorphic and anaplastic type cells can infiltrate the stomach destroying the gastric glands.
-In peripheral blood, “flower like” cells that have multilobed nucleus with basophilic cytoplasm can be observed by Giemsa staining<ref>{{Cite journal|last=Ohshima|first=Koichi|date=2007-06|title=Pathological features of diseases associated with human T-cell leukemia virus type I|url=https://pubmed.ncbi.nlm.nih.gov/17388788|journal=Cancer Science|volume=98|issue=6|pages=772–778|doi=10.1111/j.1349-7006.2007.00456.x|issn=1347-9032|pmid=17388788}}</ref>.
-==Immunophenotype==
-In most patients, tumor cells exhibit phenotype of mature CD4+ T cells by expressing CD2, CD3, CD5, CD25, CD45RO, CD29, T-cell receptor αβ, FOXP3, CD52,  and HLA-DR<ref>{{Cite journal|last=Roncador|first=G.|last2=Garcia|first2=J. F.|last3=Garcia|first3=J. F.|last4=Maestre|first4=L.|last5=Lucas|first5=E.|last6=Menarguez|first6=J.|last7=Ohshima|first7=K.|last8=Nakamura|first8=S.|last9=Banham|first9=A. H.|date=2005-12|title=FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16193085|journal=Leukemia|volume=19|issue=12|pages=2247–2253|doi=10.1038/sj.leu.2403965|issn=0887-6924|pmid=16193085}}</ref><ref>{{Cite journal|last=Ishida|first=Takashi|last2=Utsunomiya|first2=Atae|last3=Iida|first3=Shinsuke|last4=Inagaki|first4=Hiroshi|last5=Takatsuka|first5=Yoshifusa|last6=Kusumoto|first6=Shigeru|last7=Takeuchi|first7=Genji|last8=Shimizu|first8=Shigeki|last9=Ito|first9=Masato|date=2003-09-01|title=Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome|url=https://pubmed.ncbi.nlm.nih.gov/14506150|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=9|issue=10 Pt 1|pages=3625–3634|issn=1078-0432|pmid=14506150}}</ref>.
-Most cases are CD4+CD8-, but rarely, cases can be CD4-CD8+ or CD4+CD8+. A typical immunophenotype for ATLL is: CD2+, CD3+, CD4+, CD7-, CD8-, CD25+, CD30+/-, TCR αβ+<ref name=":4" />.
-Immunophenotypic characterization of CD3, CD4, CD7 , CD8, and CD25 are the minimum requirement for an ATLL diagnosis.
 {| class="wikitable sortable"
 |-
-!Finding!!Marker
+!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
+!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
 |-
-|Positive (universal)||CD2, CD3, CD5, CD4, CCD4
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|<span class="blue-text">EXAMPLE:</span>
+The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
 |-
-|Positive (subset)||CD8, CD4, CD30, FOXP3
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
-|-
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
-|Negative (universal)||CD7, CD8, TdT, TCL1, ALK1, B cell  antigens, cytotoxic molecules
+|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
+|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
+|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
+|<span class="blue-text">EXAMPLE:</span> D
+|
+|<span class="blue-text">EXAMPLE:</span>
+''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
 |-
-|Negative (subset)||CD4,CD8, ALK
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
-|}
+|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
-==Chromosomal Rearrangements (Gene Fusions)==
-Put your text here and fill in the table
+Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|<span class="blue-text">EXAMPLE:</span>
-{| class="wikitable sortable"
+Both balanced and unbalanced forms are observed by FISH (add references).
 |-
-!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''
-!Diagnostic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> N/A
-!Prognostic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
-!Therapeutic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> N/A
-!Notes
+|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
 |-
-|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+|
-EXAMPLE 30% (add reference)
+|
-|Yes
+|
-|No
+|
-|Yes
+|
-|EXAMPLE
+|
+|
-The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
+|
 |}
-<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
 Tandem duplications of  2q33.2 segments cause formation of CTLA4-CD28 and ICOS-CD28 fusion products that render prolonged co-stimulatory signals<ref name=":1">{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>.
@@ Line 151: / Line 129: @@
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
 * Chromosomal Rearrangements (Gene Fusions)
 * Individual Region Genomic Gain/Loss/LOH
 * Characteristic Chromosomal Patterns
-* Gene Mutations (SNV/INDEL)}}
+* Gene Mutations (SNV/INDEL)}}</blockquote>
 ATLL diagnosis can be made based on seropositivity for HTLV-1 and histologically and/or cytologically proven peripheral T cell lymphoma (PTCL). Diagnosis can also be made by quantifying proviral DNA loads (PVLs) in peripheral blood mononuclear cells using real time PCR. PVL of an infected person can range from 0.01 to 50% or higher. Other diagnostic criteria includes appropriate patient demographic information, hypercalcemia, skin lesions and a leukemic phase.
-The prognosis of ATLL is largely dependent on the subtype. The acute and lymphomatous subtypes are aggressive, with a median survival of 6.2 months and 10.2 months, respectively. The less-aggressive chronic and smoldering subtypes have a median survival of approximately 4.5 years<ref name=":3" />. Prognostic factors include clinical variant, age, serum calcium and LDH levels as well as detection of opportunistic infections of parasitic or viral types and p16 gene deletion and p53 mutation.
+The prognosis of ATLL is largely dependent on the subtype. The acute and lymphomatous subtypes are aggressive, with a median survival of 6.2 months and 10.2 months, respectively. The less-aggressive chronic and smoldering subtypes have a median survival of approximately 4.5 years<ref name=":3">{{Cite journal|last=Shimoyama|first=M.|date=1991-11|title=Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)|url=https://pubmed.ncbi.nlm.nih.gov/1751370|journal=British Journal of Haematology|volume=79|issue=3|pages=428–437|doi=10.1111/j.1365-2141.1991.tb08051.x|issn=0007-1048|pmid=1751370}}</ref>. Prognostic factors include clinical variant, age, serum calcium and LDH levels as well as detection of opportunistic infections of parasitic or viral types and p16 gene deletion and p53 mutation.
 As ATLL is resistant to most chemotherapy, there is no standard chemotherapy regimen. High dose combination chemotherapy and bone marrow transplantation have been tried previously<ref>{{Cite journal|last=Hishizawa|first=Masakatsu|last2=Kanda|first2=Junya|last3=Utsunomiya|first3=Atae|last4=Taniguchi|first4=Shuichi|last5=Eto|first5=Tetsuya|last6=Moriuchi|first6=Yukiyoshi|last7=Tanosaki|first7=Ryuji|last8=Kawano|first8=Fumio|last9=Miyazaki|first9=Yasushi|date=2010-08-26|title=Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study|url=https://pubmed.ncbi.nlm.nih.gov/20479287|journal=Blood|volume=116|issue=8|pages=1369–1376|doi=10.1182/blood-2009-10-247510|issn=1528-0020|pmid=20479287}}</ref>. Monoclonal antibody-based therapies against IL-2R (anti-Tac), CCR4 (mogamulizumab) and CD52 (alemtuzumab) have also been attempted along with arsenic trioxide, interferon α and zidovudine<ref>{{Cite journal|last=Hermine|first=Olivier|last2=Ramos|first2=Juan Carlos|last3=Tobinai|first3=Kensei|date=02 2018|title=A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies|url=https://pubmed.ncbi.nlm.nih.gov/29411267|journal=Advances in Therapy|volume=35|issue=2|pages=135–152|doi=10.1007/s12325-018-0658-4|issn=1865-8652|pmc=5818559|pmid=29411267}}</ref>.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==Individual Region Genomic Gain / Loss / LOH==
+==Individual Region Genomic Gain/Loss/LOH==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
 {| class="wikitable sortable"
 |-
-!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
-!Diagnostic Significance (Yes, No or Unknown)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
-!Prognostic Significance (Yes, No or Unknown)
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
-!Therapeutic Significance (Yes, No or Unknown)
+!Clinical Relevance Details/Other Notes
-!Notes
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-|EXAMPLE Loss
+|<span class="blue-text">EXAMPLE:</span> Loss
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-chr7:1- 159,335,973 [hg38]
-|EXAMPLE
 chr7
-|Yes
+|<span class="blue-text">EXAMPLE:</span>
-|Yes
+Unknown
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span> No
+|<span class="blue-text">EXAMPLE:</span>
-Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
+Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-|EXAMPLE Gain
+|<span class="blue-text">EXAMPLE:</span> Gain
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-chr8:1-145,138,636 [hg38]
-|EXAMPLE
 chr8
-|No
+|<span class="blue-text">EXAMPLE:</span>
-|No
+Unknown
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|EXAMPLE
+|
+|<span class="blue-text">EXAMPLE:</span>
-Common recurrent secondary finding for t(8;21) (add reference).
+Common recurrent secondary finding for t(8;21) (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
+|<span class="blue-text">EXAMPLE:</span>
+''ERBB2''
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
+|-
+|
+|
+|
+|
+|
+|
+|
 |}
-<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
 ATLL with high number of chromosomal imbalances is associated with poor survival<ref>{{Cite journal|last=Itoyama|first=T.|last2=Chaganti|first2=R. S.|last3=Yamada|first3=Y.|last4=Tsukasaki|first4=K.|last5=Atogami|first5=S.|last6=Nakamura|first6=H.|last7=Tomonaga|first7=M.|last8=Ohshima|first8=K.|last9=Kikuchi|first9=M.|date=2001-06-01|title=Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki|url=https://pubmed.ncbi.nlm.nih.gov/11369658|journal=Blood|volume=97|issue=11|pages=3612–3620|doi=10.1182/blood.v97.11.3612|issn=0006-4971|pmid=11369658}}</ref><ref>{{Cite journal|last=Tsukasaki|first=K.|last2=Krebs|first2=J.|last3=Nagai|first3=K.|last4=Tomonaga|first4=M.|last5=Koeffler|first5=H. P.|last6=Bartram|first6=C. R.|last7=Jauch|first7=A.|date=2001-06-15|title=Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course|url=https://pubmed.ncbi.nlm.nih.gov/11389029|journal=Blood|volume=97|issue=12|pages=3875–3881|doi=10.1182/blood.v97.12.3875|issn=0006-4971|pmid=11389029}}</ref><ref>{{Cite journal|last=Oshiro|first=Aya|last2=Tagawa|first2=Hiroyuki|last3=Ohshima|first3=Koichi|last4=Karube|first4=Kennosuke|last5=Uike|first5=Naokuni|last6=Tashiro|first6=Yukie|last7=Utsunomiya|first7=Atae|last8=Masuda|first8=Masato|last9=Takasu|first9=Nobuyuki|date=2006-06-01|title=Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16484591|journal=Blood|volume=107|issue=11|pages=4500–4507|doi=10.1182/blood-2005-09-3801|issn=0006-4971|pmid=16484591}}</ref><ref name=":2">{{Cite journal|last=Kataoka|first=Keisuke|last2=Iwanaga|first2=Masako|last3=Yasunaga|first3=Jun-Ichirou|last4=Nagata|first4=Yasunobu|last5=Kitanaka|first5=Akira|last6=Kameda|first6=Takuro|last7=Yoshimitsu|first7=Makoto|last8=Shiraishi|first8=Yuichi|last9=Sato-Otsubo|first9=Aiko|date=01 11, 2018|title=Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29084771|journal=Blood|volume=131|issue=2|pages=215–225|doi=10.1182/blood-2017-01-761874|issn=1528-0020|pmc=5757690|pmid=29084771}}</ref>.
@@ Line 271: / Line 264: @@
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==Characteristic Chromosomal Patterns==
+==Characteristic Chromosomal or Other Global Mutational Patterns==
-Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
+Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 {| class="wikitable sortable"
 |-
 !Chromosomal Pattern
-!Diagnostic Significance (Yes, No or Unknown)
+!Molecular Pathogenesis
-!Prognostic Significance (Yes, No or Unknown)
+!Prevalence -
-!Therapeutic Significance (Yes, No or Unknown)
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
-!Notes
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
 Co-deletion of 1p and 18q
-|Yes
+|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
-|No
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|EXAMPLE:
+|
+|
-See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Microsatellite instability - hypermutated
+|
+|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
+|<span class="blue-text">EXAMPLE:</span> P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
 |}
-<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
 Cytogenetic studies show that ATLL often has a complex abnormal karyotype without a single distinct abnormality. Observed recurrent abnormalities include trisomy for 3, 7 or 21 and monosomy for X as well as deletion of Y and abnormalities of chromosome 6 and 14. Chromosome 14 rearrangements involving TCRA and TCRD at 14q11 and TCL1 at 14q32 have been documented<ref>{{Cite journal|date=1987-11|title=Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/2889485|journal=Blood|volume=70|issue=5|pages=1554–1564|issn=0006-4971|pmid=2889485}}</ref>. Frequent deletions in known fragile sites have been detected in over 500 patients<ref name=":1" />.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==Gene Mutations (SNV / INDEL)==
+==Gene Mutations (SNV/INDEL)==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
 {| class="wikitable sortable"
 |-
-!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
+!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
-!'''Diagnostic Significance (Yes, No or Unknown)'''
+Common >20%, Recurrent 5-20% or Rare <5% (Disease)
-!Prognostic Significance (Yes, No or Unknown)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
-!Therapeutic Significance (Yes, No or Unknown)
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
-!Notes
+!Clinical Relevance Details/Other Notes
 |-
-|EXAMPLE: TP53; Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span>''EGFR''
-EXAMPLE:
+<br />
+|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
-EGFR; Exon 20 mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
-EXAMPLE: BRAF; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> T
-|EXAMPLE: TSG
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
-|EXAMPLE: 20% (COSMIC)
+|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
+|-
-EXAMPLE: 30% (add Reference)
+|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
-|EXAMPLE: IDH1 R123H
+<br />
-|EXAMPLE: EGFR amplification
+|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
+|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
+|<span class="blue-text">EXAMPLE:</span> P
+|
+|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|
+|-
+|
+|
+|
+|
 |
 |
 |
-|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
-<br />
-|}
-Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
-<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
 Over 10% of ATLL cases harbor mostly gain of function mutations. ATLL harbors multiple recurrent mutations in genes involved in the TCR-NF-κB pathway, tumor suppressors, transcription factors involved in cell growth and proliferation, apoptosis, and immune surveillance<ref>{{Cite journal|last=Kogure|first=Yasunori|last2=Kataoka|first2=Keisuke|date=2017-09|title=Genetic alterations in adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28627735|journal=Cancer Science|volume=108|issue=9|pages=1719–1725|doi=10.1111/cas.13303|issn=1349-7006|pmc=5581529|pmid=28627735}}</ref><ref name=":2" /><ref>{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>.
@@ Line 486: / Line 514: @@
 !Type!!Gene/Region/Other
 |-
-|Concomitant Mutations||EXAMPLE IDH1 R123H
+|Concomitant Mutations||<span class="blue-text">EXAMPLE:</span> IDH1 R123H
 |-
-|Secondary Mutations||EXAMPLE Trisomy 7
+|Secondary Mutations||<span class="blue-text">EXAMPLE:</span> Trisomy 7
 |-
-|Mutually Exclusive||EXAMPLE EGFR Amplification
+|Mutually Exclusive||<span class="blue-text">EXAMPLE:</span> EGFR Amplification
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Epigenomic Alterations==
@@ Line 502: / Line 533: @@
 ==Genes and Main Pathways Involved==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
 {| class="wikitable sortable"
 |-
 !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 |-
-|EXAMPLE: BRAF and MAP2K1; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
-|EXAMPLE: MAPK signaling
+|<span class="blue-text">EXAMPLE:</span> MAPK signaling
-|EXAMPLE: Increased cell growth and proliferation
+|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 |-
-|EXAMPLE: CDKN2A; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
-|EXAMPLE: Cell cycle regulation
+|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
-|EXAMPLE: Unregulated cell division
+|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 |-
-|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+|
-|EXAMPLE:  Histone modification, chromatin remodeling
+|
-|EXAMPLE:  Abnormal gene expression program
+|
 |}
-<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
 The most important genes involved in the development and progress of ATLL are the Tax and HBZ contributed by the HTLV-1 virus and genes listed in gene mutations table (above) from the host. The main pathways involved are TCR-NF-κB signaling by gain of function and amplifications in PLCG1, VAV1 and FYN, CD28, PRKCB, CARD11, IRF4 and RHOA; and loss of function mutations or deletions in CBLB, TRAF, TNFAIP3 and CSNK1A1<ref name=":1" />.
@@ Line 531: / Line 567: @@
 The epigenetic mechanism is also exploited to alter gene expression and promote ATLL progression as explained above.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Genetic Diagnostic Testing Methods==
@@ Line 537: / Line 576: @@
 ==Familial Forms==
 Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 ==Additional Information==
@@ Line 546: / Line 585: @@
 ==Links==
-Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
+Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
 ==References==
-(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
+(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
-'''
+<br />
 ==Notes==
-<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
+<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
+Prior Author(s):
 <nowiki>*</nowiki>''Citation of this Page'': “Adult T-cell leukaemia/lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Adult_T-cell_leukaemia/lymphoma</nowiki>.
-[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]
+[[Category:HAEM5]]
+[[Category:DISEASE]]
+[[Category:Diseases A]]

HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

Latest revision as of 12:09, 3 July 2025

Primary Author(s)*

WHO Classification of Disease

Related Terminology

Gene Rearrangements

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal or Other Global Mutational Patterns

Gene Mutations (SNV/INDEL)

Other Mutations

Epigenomic Alterations

Genes and Main Pathways Involved

Genetic Diagnostic Testing Methods

Familial Forms

Additional Information

Links

References

Notes

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