HAEM4Backup:B-Lymphoblastic Leukemia/Lymphoma with Hyperdiploidy

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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

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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

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

Sites of Involvement

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Morphologic Features

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Immunophenotype

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

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
EXAMPLE t(9;22)(q34;q11.2) EXAMPLE 3'ABL1 / 5'BCR EXAMPLE der(22) EXAMPLE 5%
EXAMPLE t(8;21)(q22;q22) EXAMPLE 5'RUNX1 / 3'RUNXT1 EXAMPLE der(8) EXAMPLE 5%

Characteristic Chromosomal Aberrations / Patterns

  • Numerical increase in chromosomes usually without structural abnormalities
  • Extra copies of chromosomes are non-random.

Genomic Gain/Loss/LOH

  • 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%)

[10] [11] [12]

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

Gene Mutations (SNV/INDEL)

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Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
EXAMPLE TP53 EXAMPLE R273H EXAMPLE Tumor Suppressor EXAMPLE LOF EXAMPLE 20%

Other Mutations

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

Epigenomics (Methylation)

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Genes and Main Pathways Involved

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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.

[13] [14][15][16]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • Pediatric patients with high hyperdiploidy have been reported to have a favorable prognosis with cure seen in >90% of children [17]
  • 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) [18]
  • Negative prognostic features include > 10 years of age, male gender, and bone marrow fibrosis [19]
  • 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% [20]
  • Familial Forms

Other Information

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Links

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References

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  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. (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.
  12. ↑ 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)
  13. ↑ 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.
  14. ↑ 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)
  15. ↑ 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)
  16. ↑ 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)
  17. ↑ 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)
  18. ↑ 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)
  19. ↑ 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)
  20. ↑ 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)

EXAMPLE Book

  1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.

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]

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