Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

Leukemia
E CsinadyE R Panzer-Grümayer

Abstract

Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is generally a clonal disease in which the number of IGH rearrangements per cell does not exceed the number of the IGH alleles on chromosome 14. Consequently, monoclonal high hyperdiploid (HeH) cases with a trisomy 14 can harbor three rearrangements, a pattern that otherwise may be misinterpreted to be oligoclonal. Oligoclonal IGH rearrangements, on the other hand, may be instable at relapse and should therefore not be used for minimal residual disease analysis. We thus investigated the association between IGH allele copy numbers and the IGH rearrangement patterns in 90 HeH BCP ALL with either two (13%) or three copies (87%) of chromosome 14. HeH cases (44%) had an oligoclonal IGH rearrangement pattern, but true oligoclonality--after correction for the respective copy number of IGH alleles--was only 16%. Monoclonal and oligoclonal HeH cases had predominantly V(H) to preexisting DJ(H) recombinations, a finding that contrasts with oligoclonal cases of other major genetic BCP ALL subgroups in which V(H) replacements prevail. We conclude that for the precise assessment and correct interpretation of clonality patterns in BCP ALL, the IGH allele copy number has to be t...Continue Reading

References

Aug 1, 1992·Immunology Today·F W AltJ Chen
Jun 28, 2003·Blood·Anthony V MoormanUNKNOWN United Kingdom Medical Research Council's Childhood Leukemia Working Party
Mar 23, 2004·Genes, Chromosomes & Cancer·Ana Teresa MaiaMel Greaves
Apr 9, 2004·The New England Journal of Medicine·Ching-Hon PuiJames R Downing
Jun 9, 2005·Genes, Chromosomes & Cancer·Kajsa PaulssonBertil Johansson
Nov 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·E Renate Panzer-GrümayerOskar A Haas

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Citations

Jun 9, 2011·Leukemia & Lymphoma·Katerina KatsibardiFotini Tzortzatou-Stathopoulou
Apr 29, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Aaron C LoganDavid B Miklos
May 6, 2009·Genes, Chromosomes & Cancer·Kajsa Paulsson, Bertil Johansson
Mar 2, 2019·Medicine, Conflict, and Survival·Frank Boulton
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Oskar A Haas

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