HAEM5:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy

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:B-Lymphoblastic Leukemia/Lymphoma with Hyperdiploidy.

(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)*

Afia Hasnain, MBBS, PhD; Yassmine Akkari, PhD, FACMG

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	B-cell lymphoid proliferations and lymphomas
Family	Precursor B-cell neoplasms
Type	B-lymphoblastic leukaemias/lymphomas
Subtype(s)	B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy

Related Terminology

Acceptable	N/A
Not Recommended	N/A

Gene Rearrangements

Although no recurrent gene fusions or rearrangements a typically found, a study found reciprocal translocations involving the IGK locus in 2 cases .

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
IGK	EXAMPLE: BCR::ABL1	EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.	t(2;19)(p11.2;q13.32)	Rare	No established significance.	No	Not described.
IGK	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.	t(2;8)(p11.2;q21.13)	Rare	No established significance.	No	Not described.

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)

• Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children
• High event-free survival (EFS) was associated with trisomy 4, 6, 17, 18, and 22, presence of triple trisomies (4, 10, 17), and high modal numbers ( > 50 chromosomes)
• Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis
• Patients with low hyperdiploidy have been reported to have a 49% EFS at 5 years compared to those with high hyperdiploidy with a five-year EFS of 71%
• Familial Forms

End of V4 Section

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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
21	Gain	Chr21	RUNX1	No established significance.	No	Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL , therefore, the presence of multiple (three to five) discrete RUNX1 signals seen when using ETV6::RUNX1 FISH probes suggests the presence of high hyperdiploidy.
X	Gain	ChrX	None	No established significance.	No
6	Gain	Chr6	None	No established significance.	No
14	Gain	Chr14	None	No established significance.	No
18	Gain	Chr18	None	Prognostic significance: has been correlated with a lower risk of relapse.	No
4	Gain	Chr4	None	The prognostic impact of the “triple trisomies”, i.e., concurrent rent +4, +10, and +17, is debated; they have been reported to be associated with low risk by the Children’s Oncology Group (COG) but not in UK trials.	No
17	Gain	Chr17	None	See prognosis section for +4 above.	No
10	Gain	Chr10	None	See prognosis section for +4 above.	No
8	Gain	Chr8	None	No established significance.	No

editv4:Genomic Gain/Loss/LOH

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

• Gains of chromosomes X, 4, 6, 10, 14, 17, 18 and 21 are most common with the following frequencies:
  • 21 (98%)
  • X (90%)
  • 6 (83%)
  • 14 (83%)
  • 18 (78%)
  • 4 (77%)
  • 17 (73%)
  • 10 (71%)
  • 8 (38%)

Chromosome Number	Gain/Loss/Amp/LOH	Region
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:0-1000000
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:0-1000000

End of V4 Section

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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
Hyperdiploid

editv4:Characteristic Chromosomal Aberrations / Patterns

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

• Numerical increase in chromosomes usually without structural abnormalities

• Extra copies of chromosomes are non-random.

End of V4 Section

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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
KRAS	EXAMPLE: Exon 18-21 activating mutations	Oncogene	Common	No	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).
NRAS	EXAMPLE: Variable LOF mutations	Oncogene	EXAMPLE: Common (breast cancer)	No		EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
FLT3	EXAMPLE: Activating mutations	Tyrosine kinase receptor	EXAMPLE: Common (melanoma)	No
PTPN11		Protein tyrosine phosphatase		No
CREBBP		Histone acetyltransferase		No
WHSC1		Histone methyltransferase		No
SUV420H1		Histone methyltransferase		No
SETD2		Histone methyltransferase		No
EZH2		Histone methyltransferase		No

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.

Epigenomic Alterations

No relevant epigenomic alterations are described. Put your text here

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

Genetic Diagnostic Testing Methods

Hyperdiploidy is readily identifiable by conventional chromosome studies, FISH and CMA. CMA studies have shown that approximately 80% of hyperdiploid cases have additional genomic abnormalities with chromosomes commonly involved being 1, 9, 11, 12, and X.

Familial Forms

No familial forms have been described. Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

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Links

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References

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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 CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

[[Copy Number and cn-LOH Abnormalities in ALL]

*Citation of this Page: “B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 10/19/2025, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_high_hyperdiploidy.