HAEM5:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy: Difference between revisions
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|Chr21 | |Chr21 | ||
|''RUNX1'' | |''RUNX1'' | ||
|No established significance | |No established significance | ||
|No | |No | ||
|Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL <ref>{{Cite journal|last=Harrison|first=Christine J.|last2=Haas|first2=Oskar|last3=Harbott|first3=Jochen|last4=Biondi|first4=Andrea|last5=Stanulla|first5=Martin|last6=Trka|first6=Jan|last7=Izraeli|first7=Shai|last8=Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group|date=2010-10|title=Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group|url=https://pubmed.ncbi.nlm.nih.gov/20701601|journal=British Journal of Haematology|volume=151|issue=2|pages=132–142|doi=10.1111/j.1365-2141.2010.08314.x|issn=1365-2141|pmid=20701601}}</ref>; therefore, the presence of multiple (three to five) discrete ''RUNX1'' signals seen when using ''ETV6''::''RUNX1'' FISH probes suggests the presence of high hyperdiploidy. | |Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL <ref>{{Cite journal|last=Harrison|first=Christine J.|last2=Haas|first2=Oskar|last3=Harbott|first3=Jochen|last4=Biondi|first4=Andrea|last5=Stanulla|first5=Martin|last6=Trka|first6=Jan|last7=Izraeli|first7=Shai|last8=Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group|date=2010-10|title=Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group|url=https://pubmed.ncbi.nlm.nih.gov/20701601|journal=British Journal of Haematology|volume=151|issue=2|pages=132–142|doi=10.1111/j.1365-2141.2010.08314.x|issn=1365-2141|pmid=20701601}}</ref>; therefore, the presence of multiple (three to five) discrete ''RUNX1'' signals seen when using ''ETV6''::''RUNX1'' FISH probes suggests the presence of high hyperdiploidy. | ||
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|N/A | |N/A | ||
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|Chr17 | |Chr17 | ||
|None | |None | ||
|''See prognosis section for +4 above | |''See prognosis section for +4 above'' | ||
|No | |No | ||
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|Chr10 | |Chr10 | ||
|None | |None | ||
|''See prognosis section for +4 above | |''See prognosis section for +4 above'' | ||
|No | |No | ||
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|No | |No | ||
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Revision as of 09:02, 11 November 2025
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 ClassificationThis 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)*
Miguel Gonzalez Mancera, MD
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
No recurrent gene rearrangements have been described[1].
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: BCR::ABL1 | EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. | ||||||
| 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. |
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 [2]
- 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) [3]
- Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis [4]
- 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% [5]
- Familial Forms
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 |
|---|---|---|---|---|---|---|
| 21 | Gain | Chr21 | RUNX1 | No established significance | No | Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL [6]; 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 | N/A |
| 6 | Gain | Chr6 | None | No established significance | No | N/A |
| 14 | Gain | Chr14 | None | No established significance | No | N/A |
| 18 | Gain | Chr18 | None | Prognostic significance: has been correlated with a lower risk of relapse[7]. | No | N/A |
| 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)[8], but not in UK trials[7]. | No | N/A |
| 17 | Gain | Chr17 | None | See prognosis section for +4 above | No | N/A |
| 10 | Gain | Chr10 | None | See prognosis section for +4 above | No | N/A |
| 8 | Gain | Chr8 | None | No established significance | No | N/A |
editv4:Genomic Gain/Loss/LOHThe 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
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 |
|---|---|---|---|---|---|
| Hyperdiploid | Although pathogenetic mechanisms are poorly understood, chromosomal gains are early events in the pathogenesis of B-ALL/LBL with high hyperdiploidy and are the main driver[1]. | Common | D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH
P: B-ALL/LBL with high-hyperdiploidy has a very favorable prognosis, with long-term overall survival in > 90% of children T: N/A |
No | Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children[2].
Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis[4]. More recent studies have validated a risk profile determining that outcome appears to be linked to specific chromosomal gains[12]. |
editv4:Characteristic Chromosomal Aberrations / PatternsThe 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
Gene Mutations (SNV/INDEL)
Nine genes have been found to be recurrently mutated and were also either mutated more frequently than expected by chance or targeted by structural events[10]. 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
|
Nonsynonymous single nucleotide variant (SNV) in known codon 12 and 13 hotspot region, and additional mutations in codons 116 and 146[11] | Oncogene | Common | No | No | KRAS codons 117 and 146 may be new recurrent mutational hotspots in high hyperdiploid ALL. |
| NRAS
|
Nonsynonymous SNV | Oncogene | Recurrent | No | No | N/A |
| FLT3 | Nonsynonymous SNV, nonframeshift insertion, nonframeshift deletion, nonframeshift substitution | Tyrosine kinase receptor | Recurrent | No | No | N/A |
| PTPN11 | Nonsynonymous SNV | Protein tyrosine phosphatase | Recurrent | No | No | N/A |
| CREBBP | Nonsynonymous SNV, frameshift insertion, splice site | Histone acetyltransferase | Recurrent | No | No | CREBBP has been reported to be mutated in a high proportion of relapsing high hyperdiploid childhood ALLs[13]. |
| WHSC1 | Nonsynonymous SNV | Histone methyltransferase | Recurrent | No | No | N/A |
| SUV420H1 | Nonsynonymous SNV | Histone methyltransferase | Rare | No | No | N/A |
| SETD2 | Frameshift insertion | Histone methyltransferase | Rare | No | No | N/A |
| EZH2 | Nonsynonymous SNV | Histone methyltransferase | Rarre | No | No | N/A |
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 have been 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 |
|---|---|---|
| FLT3, NRAS, KRAS and PTPN11[14]; Activating mutations | Receptor tyrosine kinase (RTK)-RAS signaling | Increased proliferation, differentiation, and survival |
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
Put your text here
Links
Put your links here (use link icon at top of page)
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 WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print] (5th ed.), International Agency for Research on Cancer (2022) https://tumourclassification.iarc.who.int/chapters/63
- ↑ 2.0 2.1 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) - ↑ 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) - ↑ 4.0 4.1 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) - ↑ 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) - ↑ Harrison, Christine J.; et al. (2010-10). "Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group". British Journal of Haematology. 151 (2): 132–142. doi:10.1111/j.1365-2141.2010.08314.x. ISSN 1365-2141. PMID 20701601. Check date values in:
|date=(help) - ↑ 7.0 7.1 Moorman, Anthony V.; et al. (2010-05). "Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial". The Lancet. Oncology. 11 (5): 429–438. doi:10.1016/S1470-2045(10)70066-8. ISSN 1474-5488. PMID 20409752. Check date values in:
|date=(help) - ↑ Schultz, Kirk R.; et al. (2007-02-01). "Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)". Blood. 109 (3): 926–935. doi:10.1182/blood-2006-01-024729. ISSN 0006-4971. PMC 1785141. PMID 17003380.
- ↑ 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) - ↑ 10.0 10.1 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.
- ↑ 11.0 11.1 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) - ↑ Enshaei, Amir; et al. (2021-11). "Defining low-risk high hyperdiploidy in patients with paediatric acute lymphoblastic leukaemia: a retrospective analysis of data from the UKALL97/99 and UKALL2003 clinical trials". The Lancet. Haematology. 8 (11): e828–e839. doi:10.1016/S2352-3026(21)00304-5. ISSN 2352-3026. PMC 8567211 Check
|pmc=value (help). PMID 34715050 Check|pmid=value (help). Check date values in:|date=(help) - ↑ Inthal, A.; et al. (2012-08). "CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia". Leukemia. 26 (8): 1797–1803. doi:10.1038/leu.2012.60. ISSN 1476-5551. PMC 4194312. PMID 22388726. Check date values in:
|date=(help) - ↑ 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) - ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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 11/11/2025, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_high_hyperdiploidy.