ALK-negative anaplastic large cell lymphoma

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

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:Anaplastic Large Cell Lymphoma, ALK-Negative.

(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)*

Miguel Gonzalez Mancera, MD

Sumire Kitahara, MD

Cedars-Sinai, Los Angeles, CA

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 Anaplastic large cell lymphoma
Subtype(s) ALK-negative anaplastic large cell lymphoma

Related Terminology

Acceptable Anaplastic large cell lymphoma, ALK-negative
Not Recommended N/A

Gene Rearrangements

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
Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
*t(6;7)(p25.3;q32.3) DUSP22/FRA7H[1] DUSP22/FRA7H fusion protein 30%[2] No Yes No
  • * These rearrangements are considered mutually exclusive; however, a single case with both DUSP22 and TP63 rearrangement has been described[3]. Can also be seen in a fraction of other PTCL.
  • 5-year overall survival > 90%
  • Therapeutic Implications
    • Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site
    • High dose chemotherapy and autologous stem cell transplantation for remission
    • DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
    • Theoretical:
      • Ruxolitinib may be used to target JAK-STAT pathway[4][5] (not FDA-approved)
      • Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway[5][6]
*t(3;3)(q22;q26.2), inv(3)(q26q28) TP63/TBL1XR1[7] TP63/TBL1XR1 fusion protein 8%[2] No Yes No
  • *See t(6;7) notes
  • 5-year overall survival 17%
t(10;19)(q24;p13) NFKB2/TYK2 NFKB2/TYK2 fusion protein rare[8] No No No
  • 5-year overall survival 42% for cases lacking all DUSP22, TP63 and ALK rearrangements[2][9]
t(1;19)(p34;p13) PABPC4/TYK2 PABPC4/TYK2 fusion protein rare[8] No No No
t(6;10)(q22;q24) NFKB2/ROS1 NFKB2/ROS1 fusion protein rare[8] No No No


editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.
Chromosomal Rearrangement[10][11] Genes in Fusion (5’ or 3’ Segments) Prevalence
*t(6;7)(p25.3;q32.3) DUSP22/FRA7H[1] 30%[2]
*t(3;3)(q22;q26.2), inv(3)(q26q28) TP63/TBL1XR1[7] 8%[2]
t(10;19)(q24;p13) NFKB2/TYK2 rare[8]
t(1;19)(p34;p13) PABPC4/TYK2 rare[8]
t(6;10)(q22;q24) NFKB2/ROS1 rare[8]

* These rearrangements are considered mutually exclusive; however, a single case with both DUSP22 and TP63 rearrangement has been described[3]. Can also be seen in a fraction of other PTCL.

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)
  • Diagnosis
    • In general, ALK(-) ALCL has a worse prognosis when compared to ALK (+) ALCL[12]
    • ALK(-) ALCL has shown superior prognosis when compared to PTCL, NOS. The 5-year failure-free survival rate was 36% vs 20%, and overall survival rate was 49% vs 32%[13]
  • Prognosis
    • When compared to ALK(+) ALCL, ALK(-) ALCL has a generally poorer prognosis, however:
      • When stratified for age, prognosis between ALK(-) and ALK(+) ALCL appears similar [13][14]
    • 5-year overall survival > 90% for DUSP22-rearranged ALK(-) ALCL, 17% for TP63-rearranged ALK(-) ALCL, and 42% for cases lacking all DUSP22, TP63 and ALK rearrangements[2][9]
    • Patients with 6q21/PRDM1 and/or 17p loss showed an inferior outcome than patients with normal 6q21 and 17p; not clear if mainly due to TP53 deletion due to study size[15]
      • Often concomitant loss and seen in almost a quarter of cases
    • Mutations with significantly shorter OS compared to wild-type[16]
    • Prognostic significance of ERB4 and COL29A1 co-expressing subtypes unclear [17]
  • Therapeutic Implications
    • Multi-agent chemotherapy (CHOEP or CHOP-based) as first-line, with or without radiotherapy of involved site
    • High dose chemotherapy and autologous stem cell transplantation for remission
    • DUSP22 subtype may not gain additional benefit from autologous stem cell transplantation in first remission
    • Theoretical:
      • Ruxolitinib may be used to target JAK-STAT pathway[4][5] (not FDA-approved)
      • Bromodomain and extra-terminal proteins (BET) inhibitors may target ERBB4 pathway[5][6]
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.


Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
1q Gain No No No
  • Prevalence 30%
  • Numerous genes affected
6p Gain 25.3 No No No
  • Prevalence 30%
  • Gene affected: DUSP22
8q Gain 24.22 No No No
  • Prevalence 16-23%
  • Genes affected: NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1
1p Loss 13.3-p12

36.33-36.32

No No No
  • Prevalence 19-26%
6q Loss > CN-LOH 21 No No No
  • Prevalence 35%
  • Genes affected: PRDM1, ATG5
10p Loss 11.23-p11.22 No No No
  • Prevalence 23%
13q Loss 32.3-q33.3 No No No
  • Prevalence 23%
  • Genes affected: CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1
16q Loss 23.2 No No No
  • Prevalence 29%
  • Genes affected: MAF, WWOX
17p Loss 13.3-p12 No Yes?** No
  • Prevalence: 42%
  • Gene affected: TP53
editv4:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.

The pattern of genomic copy number changes and loss of heterozygosity have been described[15][18][19]:

  • In general, recurrent lesions are more common in ALK(-) than ALK(+) disease
  • 6q21 losses associated with 17p deletions seen in ~25% of cases of ALK(-) ALCL[15]
  • None are diagnostically helpful for the distinction between ALK(-) ALCL from other entities
Chromosome Number Gain/Loss/Amp/LOH Region Genes Prevalence
1q Gain numerous 30%
6p Gain 25.3 DUSP22 30%
8q Gain 24.22 NDRG1, PHF20L1, SLA, ST3GAL1, TG, WISP1 16-23%
1p Loss 13.3-p12

36.33-36.32

26%

19%

6q Loss > CN-LOH;

See also below for somatic mutations

21 PRDM1, ATG5 35%
10p Loss 11.23-p11.22 23%
13q Loss 32.3-q33.3 CDC16, CUL4A,FOXO1A, BRCA2, LHFP, LCP1 23%
16q Loss 23.2 MAF, WWOX 29%
17p Loss 13.3-p12 TP53 42%
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 Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
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.
  • Gene expression profiling and comparative genomic hybridization studies have shown that ALK(+) and ALK(-) ALCL share restricted genomic signatures and/or preferential genomic aberrations[20][21][22]
  • Several genes are similarly expressed in ALK(+) and ALK(-) samples, suggesting a common ALCL signature, that permit differential diagnosis of ALCL from PTCL-NOS[23]
  • See other sections.
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.


Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
TP53 TSG 23%[16] No N/A No Yes No
STAT3 Oncogene 26%[16] No N/A No Yes No
  • Ruxolitinib may be used to target JAK-STAT pathway (not FDA-approved)[4]
JAK1 Oncogene 26%[16] No N/A No Yes No
PRDM1/BLIMP1[15] TSG 6% No N/A No No No
NOTCH1[24] Oncogene 15% No No No No No
KMT2D[16] TSG 20% No No No No No

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.


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.
Gene Presumed mechanism Frequency Notes
STAT3*[8][16] Activating 10-26% Not seen in PTCL-NOS[8] or ALK+ ALCL[8][16]
JAK1*[8][16] Activating 15-26% Not seen in PTCL-NOS[8] or ALK+ ALCL[8][16]
PRDM1/BLIMP1[15] Tumor suppressor 6% (2/31)
NOTCH1[24] Activating 15%
TP53[16] Tumor suppressor 23%
KMT2D[16] Tumor suppressor 20%

*Double mutated for JAK1+STAT3 in 7-11%[8][16]

Other mutations

  • Epigenetic modifier genes: TET2[8][16]
  • Uncommon: FAS, STIM2[8]; LRP1B (9%), EPHA5[16]
End of V4 Section

Epigenomic Alterations

  • See above mutations in epigenetic modifier genes

Genes and Main Pathways Involved

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

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
STAT3[8] JAK-STAT pathway Increased cell growth and proliferation
NFkB2-ROS1 fusion[8] JAK-STAT pathway Increased cell growth and proliferation
NFkB2-TYK2 fusion[8] JAK-STAT pathway Increased cell growth and proliferation
editv4:Genes and Main Pathways Involved
The content below was from the old template. Please incorporate above.
  • JAK-STAT[8]
    • STAT3 mutants are constitutively phosphorylated
    • JAK1 mutants lead to the constitutive phosphorylation of STAT and synergize with STAT3 mutants
    • When JAK/STAT3 mutations absent, NFkB2-ROS1 and NFkB2-TYK2 fusions may constitutively activate STAT pathway
End of V4 Section

Genetic Diagnostic Testing Methods

  • Morphologic and immunophenotypic characterization
    • Strong CD30 staining of equal intensity help distinguish from PTCL, NOS, classic Hodgkin lymphoma, diffuse large B-cell lymphoma, and monomorphic epitheliotropic intestinal T-cell lymphoma
    • Exclusion of ALK(+) ALCL cases by immunostain for ALK
    • P63 immunostain to identify TP63 rearranged. Immunophenotyping is not sensitive and is thus used as screening before FISH analysis. A ≥ 30% threshold yields 100% sensitivity[25]
  • Presence of STAT3 and/or JAK1 mutations seem to favor ALK(-) ALCL over PTCL-NOS[8]
  • FISH studies necessary to subtype:
    • DUSP22 (IRF4/DUSP22) break-apart probe
    • TP63 rearrangement
  • ERBB4(+) cases may be identified using digital droplet PCR or immunostaining for MMP9 (a protein highly correlated with ERBB4 expression)
    • Not routinely performed

Familial Forms

  • Not described

Additional Information

This disease is defined/characterized as detailed below:

Anaplastic large cell lymphomas (ALCL), ALK-negative, is a CD30+ T-cell lymphoma that is morphologically and immunophenotypically indistinguishable (but lacks ALK protein expression) from ALK(+) ALCL[26][12]

  • Three major molecular subtypes of ALK (-) ALCL[26][12]:
    • DUSP22-rearranged subtype (30%)
    • TP63-rearranged subtype (8%)
    • Triple-negative subtype (DUSP22 negative, TP63 negative, ALK negative)
    • Emerging subtypes:
      • ERBB4 expression (~25%): mutually exclusive with other rearrangements (TP63, DUSP22, ROS or TYK translocations)[17]

The epidemiology/prevalence of this disease is detailed below:

  • More common in adults than children (peak incidence 6th decade of life)[27]
  • Less than 3% of all Non-Hodgkin's lymphoma[27]
  • M:F 1.5:1[27]

The clinical features of this disease are detailed below:

Signs and symptoms - B-symptoms (weight loss, fever, night sweats)[27]; Peripheral and/or Lymphadenopathy[27]; Most patients present with advanced stage disease[27]

Laboratory findings - Not specific

The sites of involvement of this disease are detailed below:

  • Nodal (predominantly abdominal lymphadenopathy) in a sinusoidal pattern
  • Extranodal (skin, soft tissue, gastrointestinal, bone) in about 20% of cases
    • If involving the skin or GI tract, cases must be distinguished from primary cutaneous ALCL or CD30+ enteropathy-associated/other intestinal T-cell lymphomas, respectively

The morphologic features of this disease are detailed below:

  • Tissue effacement by cohesive sheets of large, pleomorphic neoplastic cells, with or without prominent nucleoli, with varying proportions of hallmark cells
  • "Hallmark cells"
    • Lymphoma cells characterized by eccentric, horseshoe-shaped or kidney-shaped nuclei, often with eosinophilic cytoplasm accentuated near the nucleus
    • Usually large in size, but may also be smaller
    • Less common that in classic variant of ALK (+) ALCL
  • DUSP22-rearranged subtype tends to lack large pleomorphic cells and show smaller, monomorphic cells with central nuclear pseudoinclusions (doughnut cells)
  • Intrasinusoidal growth pattern seen in cases with preserved nodal architecture

The immunophenotype of this disease is detailed below:

Immunohistochemical patterns vary by subtype[27][28][2]

DUSP22-rearranged subtype

Finding Marker
Positive (universal) CD30*, CD43 (almost universally)
Negative (universal) ALK, TP63, EBER, LMP-1
Positive (frequent) CD2, CD3, CD4+ cases more common than CD8, CD5, Clusterin
Negative (frequent) TIAI, granzyme B, perforin, EMA, PAX5

*Strong and diffuse CD30 staining; should be equal intensity in all cells

TP63-rearranged subtype

Finding Marker
Positive (universal) CD30*, CD43 (almost universally), P63, CD4+ cases more common than CD8
Negative (universal) ALK, EBER, LMP-1
Positive (frequent) CD2, CD3, CD4, CD5, TIA1, granzyme B, perforin, clusterin
Negative (very frequent) EMA

Triple-negative subtype

Finding Marker
Positive (universal) CD30*, CD43 (almost universally), CD2, CD3, CD4+ cases more common than CD8, CD5, TIA1, granzyme B, perforin, EMA
Negative (universal) ALK, P63, EBER, LMP-1
Positive (common) EMA, clusterin
Negative (frequent) PAX5, CD20, CD79a, CD15

Links

  • See references.

References

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  1. ↑ 1.0 1.1 Feldman, Andrew L.; et al. (2011-01-20). "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing". Blood. 117 (3): 915–919. doi:10.1182/blood-2010-08-303305. ISSN 1528-0020. PMC 3035081. PMID 21030553.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Er, Parrilla Castellar; et al. (2014). "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes". doi:10.1182/blood-2014-04-571091. PMC 4148769. PMID 24894770.CS1 maint: PMC format (link)
  3. ↑ 3.0 3.1 K, Karube; et al. (2020). ""Double-hit" of DUSP22 and TP63 rearrangements in anaplastic large cell lymphoma, ALK-negative". PMID 32106310 Check |pmid= value (help).
  4. ↑ 4.0 4.1 4.2 R, Roskoski (2016). "Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases". PMID 27473820.
  5. ↑ 5.0 5.1 5.2 5.3 E, Mereu; et al. (2017). "The heterogeneous landscape of ALK negative ALCL". doi:10.18632/oncotarget.14503. PMC 5392347. PMID 28061468.CS1 maint: PMC format (link)
  6. ↑ 6.0 6.1 A, Chaidos; et al. (2015). "Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence". doi:10.1177/2040620715576662. PMC 4480520. PMID 26137204.CS1 maint: PMC format (link)
  7. ↑ 7.0 7.1 Vasmatzis, George; et al. (2012-09-13). "Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas". Blood. 120 (11): 2280–2289. doi:10.1182/blood-2012-03-419937. ISSN 1528-0020. PMC 5070713. PMID 22855598.
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 8.21 8.22 8.23 R, Crescenzo; et al. (2015). "Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma". doi:10.1016/j.ccell.2015.03.006. PMC 5898430. PMID 25873174.CS1 maint: PMC format (link)
  9. ↑ 9.0 9.1 Mb, Pedersen; et al. (2017). "DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study". doi:10.1182/blood-2016-12-755496. PMC 5533203. PMID 28522440.CS1 maint: PMC format (link)
  10. ↑ Pileri, Stefano (2011-05-01). "Faculty Opinions recommendation of Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing".
  11. ↑ Da, Wada; et al. (2011). "Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies". doi:10.1038/modpathol.2010.225. PMC 3122134. PMID 21169992.CS1 maint: PMC format (link)
  12. ↑ 12.0 12.1 12.2 Sh, Swerdlow; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.CS1 maint: PMC format (link)
  13. ↑ 13.0 13.1 Kj, Savage; et al. (2008). "ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project". PMID 18385450.
  14. ↑ D, Sibon; et al. (2012). "Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials". PMID 23045585.
  15. ↑ 15.0 15.1 15.2 15.3 15.4 M, Boi; et al. (2013). "PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma". PMID 24004669.
  16. ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 16.13 16.14 16.15 Lobello, Cosimo; et al. (2020-11-27). "STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma". Leukemia: 1–6. doi:10.1038/s41375-020-01093-1. ISSN 1476-5551.
  17. ↑ 17.0 17.1 I, Scarfò; et al. (2016). "Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts". PMID 26463425.
  18. ↑ G, Vasmatzis; et al. (2012). "Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas". doi:10.1182/blood-2012-03-419937. PMC 5070713. PMID 22855598.CS1 maint: PMC format (link)
  19. ↑ Y, Zeng; et al. (2016). "Genetics of anaplastic large cell lymphoma". doi:10.3109/10428194.2015.1064530. PMC 4732699. PMID 26104084.CS1 maint: PMC format (link)
  20. ↑ Thompson, Mary Ann; et al. (2005-05). "Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas". Human Pathology. 36 (5): 494–504. doi:10.1016/j.humpath.2005.03.004. ISSN 0046-8177. PMID 15948116. Check date values in: |date= (help)
  21. ↑ Piccaluga, Pier Paolo; et al. (2007-03). "Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets". The Journal of Clinical Investigation. 117 (3): 823–834. doi:10.1172/JCI26833. ISSN 0021-9738. PMC 1794115. PMID 17304354. Check date values in: |date= (help)
  22. ↑ Salaverria, Itziar; et al. (2008-03). "Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas". British Journal of Haematology. 140 (5): 516–526. doi:10.1111/j.1365-2141.2007.06924.x. ISSN 1365-2141. PMID 18275429. Check date values in: |date= (help)
  23. ↑ Piva, Roberto; et al. (2010-03-20). "Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (9): 1583–1590. doi:10.1200/JCO.2008.20.9759. ISSN 1527-7755. PMID 20159827.
  24. ↑ 24.0 24.1 Larose, Hugo; et al. (2020-04-23). "Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target". Haematologica. doi:10.3324/haematol.2019.238766. ISSN 1592-8721.
  25. ↑ X, Wang; et al. (2017). "Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping". doi:10.1016/j.humpath.2017.01.003. PMC 5518937. PMID 28153507.CS1 maint: PMC format (link)
  26. ↑ 26.0 26.1 Ad, Attygalle; et al. (2014). "Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology". doi:10.1111/his.12251. PMC 6364972. PMID 24128129.CS1 maint: PMC format (link)
  27. ↑ 27.0 27.1 27.2 27.3 27.4 27.5 27.6 G, Hapgood; et al. (2015). "The biology and management of systemic anaplastic large cell lymphoma". PMID 25869285.
  28. ↑ M, Herling; et al. (2004). "Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria". PMID 15116326.


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*Citation of this Page: “ALK-negative anaplastic large cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 07/3/2025, https://ccga.io/index.php/HAEM5:ALK-negative_anaplastic_large_cell_lymphoma.

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