Compendium of Cancer Genome Aberrations

B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy

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Haematolymphoid Tumours (5th ed.)

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This page was converted to the new template on 2023-12-04. The original page can be found at HAEM4:B-Lymphoblastic Leukemia/Lymphoma with Hyperdiploidy.

Primary Author(s)*

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

Cancer Category / Type

B-Lymphoblastic Leukemia/Lymphoma

Cancer Sub-Classification / Subtype

B-Lymphoblastic Leukemia/Lymphoma with hyperdiploidy

Definition / Description of Disease

B-ALL with hyperdiploidy is a neoplasm of lymphoblasts committed to the B-cell lineage whose blasts contain >50 chromosome (usually <66), typically without translocations or other structural alterations.  


In the context of B-ALL, hyperdiploidy is further subdivided into two groups including low hyperdiploidy (47–50 chromosomes) and high hyperdiploidy ( > 50 chromosomes) with some studies further defining the high hyperdiploid subgroup as those with a modal chromosome number of 51–68. [1] [2] [3] [4]

Synonyms / Terminology

Put your text here (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)

Epidemiology / Prevalence

The incidence of hyperdiploidy in B-ALL decreases with age: [5][6][7][8][9]

  • approximately 25% of pediatric patients (ages 1–9 years)
  • approximately 10% of adolescents (ages 10–15 years)
  • approximately 5–7% of adults (age > 19 years)

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table)

Signs and Symptoms EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Fatigue

EXAMPLE Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE Cytopenias

EXAMPLE Lymphocytosis (low level)


editv4:Clinical Features
The content below was from the old template. Please incorporate above.

The presenting features are generally similar to those seen in patients with other ALLs.

Sites of Involvement

Put your text here (Instruction: Indicate physical sites; Example: nodal, extranodal, bone marrow)

Morphologic Features

Put your text here

Immunophenotype

Put your text here and/or fill in the table

Finding Marker
Positive (universal) CD19, CD10
Positive (subset) CD34
Negative (universal) CD45
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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
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).


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 [10]
  • 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) [11]
  • Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis [12]
  • 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% [13]
  • Familial Forms

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (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.)

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
EXAMPLE

7

EXAMPLE Loss EXAMPLE

chr7:1- 159,335,973 [hg38]

EXAMPLE

chr7

Yes Yes 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 reference).

EXAMPLE

8

EXAMPLE Gain EXAMPLE

chr8:1-145,138,636 [hg38]

EXAMPLE

chr8

No No No EXAMPLE

Common recurrent secondary finding for t(8;21) (add reference).

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%)

[14] [15] [16]

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

Characteristic Chromosomal Patterns

Put your text here (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)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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.

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 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.)

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
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in 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.

[17] [18][19][20]

Familial Forms

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

(use the "Cite" icon at the top of the page) (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. 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.)

  1. ↑ Groeneveld-Krentz, Stefanie; et al. (04 2019). "Aneuploidy in children with relapsed B-cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse". British Journal of Haematology. 185 (2): 266–283. doi:10.1111/bjh.15770. ISSN 1365-2141. PMID 30714092. Check date values in: |date= (help)
  2. ↑ Chessels, J. M.; et al. (1997-10). "Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia". British Journal of Haematology. 99 (1): 93–100. doi:10.1046/j.1365-2141.1997.3493163.x. ISSN 0007-1048. PMID 9359508. Check date values in: |date= (help)
  3. ↑ Reismüller, Bettina; et al. (06 2017). "High hyperdiploid acute lymphoblastic leukemia (ALL)-A 25-year population-based survey of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group". Pediatric Blood & Cancer. 64 (6). doi:10.1002/pbc.26327. ISSN 1545-5017. PMID 27804199. Check date values in: |date= (help)
  4. ↑ Paulsson, Kajsa; et al. (2015-06). "The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia". Nature Genetics. 47 (6): 672–676. doi:10.1038/ng.3301. ISSN 1546-1718. PMID 25961940. Check date values in: |date= (help)
  5. ↑ Paulsson, Kajsa; et al. (2013-09). "High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols". Haematologica. 98 (9): 1424–1432. doi:10.3324/haematol.2013.085852. ISSN 1592-8721. PMC 3762100. PMID 23645689. Check date values in: |date= (help)
  6. ↑ Paulsson, Kajsa; et al. (2010-12-14). "Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21719–21724. doi:10.1073/pnas.1006981107. ISSN 1091-6490. PMC 3003126. PMID 21098271.
  7. ↑ Paulsson, Kajsa; et al. (2009-08). "High hyperdiploid childhood acute lymphoblastic leukemia". Genes, Chromosomes & Cancer. 48 (8): 637–660. doi:10.1002/gcc.20671. ISSN 1098-2264. PMID 19415723. Check date values in: |date= (help)
  8. ↑ Mullighan, Charles G. (2014-12-05). "The genomic landscape of acute lymphoblastic leukemia in children and young adults". Hematology. American Society of Hematology. Education Program. 2014 (1): 174–180. doi:10.1182/asheducation-2014.1.174. ISSN 1520-4383. PMID 25696852.
  9. ↑ Okamoto, Ryoko; et al. (2010-09). "Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia". Haematologica. 95 (9): 1481–1488. doi:10.3324/haematol.2009.011114. ISSN 1592-8721. PMC 2930948. PMID 20435627. Check date values in: |date= (help)
  10. ↑ Paulsson, Kajsa; et al. (2013-09). "High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols". Haematologica. 98 (9): 1424–1432. doi:10.3324/haematol.2013.085852. ISSN 1592-8721. PMC 3762100. PMID 23645689. Check date values in: |date= (help)
  11. ↑ Paulsson, Kajsa; et al. (2013-09). "High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols". Haematologica. 98 (9): 1424–1432. doi:10.3324/haematol.2013.085852. ISSN 1592-8721. PMC 3762100. PMID 23645689. Check date values in: |date= (help)
  12. ↑ Paulsson, Kajsa; et al. (2013-09). "High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols". Haematologica. 98 (9): 1424–1432. doi:10.3324/haematol.2013.085852. ISSN 1592-8721. PMC 3762100. PMID 23645689. Check date values in: |date= (help)
  13. ↑ Chessels, J. M.; et al. (1997-10). "Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia". British Journal of Haematology. 99 (1): 93–100. doi:10.1046/j.1365-2141.1997.3493163.x. ISSN 0007-1048. PMID 9359508. Check date values in: |date= (help)
  14. ↑ Paulsson, Kajsa; et al. (2013-09). "High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols". Haematologica. 98 (9): 1424–1432. doi:10.3324/haematol.2013.085852. ISSN 1592-8721. PMC 3762100. PMID 23645689. Check date values in: |date= (help)
  15. ↑ Paulsson, Kajsa; et al. (2010-12-14). "Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21719–21724. doi:10.1073/pnas.1006981107. ISSN 1091-6490. PMC 3003126. PMID 21098271.
  16. ↑ Paulsson, Kajsa; et al. (2009-08). "High hyperdiploid childhood acute lymphoblastic leukemia". Genes, Chromosomes & Cancer. 48 (8): 637–660. doi:10.1002/gcc.20671. ISSN 1098-2264. PMID 19415723. Check date values in: |date= (help)
  17. ↑ Paulsson, Kajsa; et al. (2010-12-14). "Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21719–21724. doi:10.1073/pnas.1006981107. ISSN 1091-6490. PMC 3003126. PMID 21098271.
  18. ↑ Schraders, Margit; et al. (2009-05). "High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage". Cancer Genetics and Cytogenetics. 191 (1): 27–33. doi:10.1016/j.cancergencyto.2009.01.002. ISSN 1873-4456. PMID 19389505. Check date values in: |date= (help)
  19. ↑ Steeghs, Elisabeth M. P.; et al. (03 15, 2019). "Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia". Scientific Reports. 9 (1): 4634. doi:10.1038/s41598-019-41078-4. ISSN 2045-2322. PMC 6420659. PMID 30874617. Check date values in: |date= (help)
  20. ↑ Lejman, Monika; et al. (08 2019). "Microarray testing as an efficient tool to redefine hyperdiploid paediatric B-cell precursor acute lymphoblastic leukaemia patients". Leukemia Research. 83: 106163. doi:10.1016/j.leukres.2019.05.013. ISSN 1873-5835. PMID 31202078. Check date values in: |date= (help)

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 12/4/2023, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_high_hyperdiploidy.

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