Post-Transformation IGHV-IGHD-IGHJ Mutations in Chronic Lymphocytic Leukemia B Cells: Implications for Mutational Mechanisms and Impact on Clinical Course.

Frontiers in Oncology
Davide BagnaraNicholas Chiorazzi

Abstract

Analyses of IGHV gene mutations in chronic lymphocytic leukemia (CLL) have had a major impact on the prognostication and treatment of this disease. A hallmark of IGHV-mutation status is that it very rarely changes clonally over time. Nevertheless, targeted and deep DNA sequencing of IGHV-IGHD-IGHJ regions has revealed intraclonal heterogeneity. We used a DNA sequencing approach that achieves considerable depth and minimizes artefacts and amplification bias to identify IGHV-IGHD-IGHJ subclones in patients with prolonged temporal follow-up. Our findings extend previous studies, revealing intraclonal IGHV-IGHD-IGHJ diversification in almost all CLL clones. Also, they indicate that some subclones with additional IGHV-IGHD-IGHJ mutations can become a large fraction of the leukemic burden, reaching numerical criteria for monoclonal B-cell lymphocytosis. Notably, the occurrence and complexity of post-transformation IGHV-IGHD-IGHJ heterogeneity and the expansion of diversified subclones are similar among U-CLL and M-CLL patients. The molecular characteristics of the mutations present in the parental, clinically dominant CLL clone (CDC) differed from those developing post-transformation (post-CDC). Post-CDC mutations exhibit significant...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jan 1, 1997·International Reviews of Immunology·K N PotterJ D Capra
Jan 9, 1998·The American Journal of Surgical Pathology·M BonatoC De Wolf-Peeters
Oct 28, 1998·The Journal of Clinical Investigation·F FaisN Chiorazzi
Nov 7, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L JuompanM Zouali
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L G Cowell, T B Kepler
Mar 4, 2000·International Immunology·M N NeshatJ Braun
Mar 5, 2003·Annual Review of Immunology·Nicholas Chiorazzi, Manlio Ferrarini
Jun 21, 2005·The Journal of Clinical Investigation·Güllü GörgünJohn G Gribben
Jul 27, 2005·British Journal of Haematology·Gerald E MartiUNKNOWN International Familial CLL Consortium
Mar 4, 2006·British Journal of Haematology·Davide BagnaraFranco Fais
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessie F FecteauSonia Néron
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chungwen WeiIñaki Sanz
Feb 14, 2009·The New England Journal of Medicine·Ola LandgrenNeil E Caporaso
Aug 25, 2009·Mechanisms of Ageing and Development·Giuseppina Colonna-RomanoCalogero Caruso
Jan 12, 2011·The Journal of Experimental Medicine·Daniel O GriffinThomas L Rothstein
Jun 15, 2011·Nucleic Acids Research·Mohamed UdumanSteven H Kleinstein
May 30, 2012·Nucleic Acids Research·Gur YaariSteven H Kleinstein
Oct 24, 2012·The Journal of Experimental Medicine·Marc SeifertRalf Küppers
Mar 13, 2014·Bioinformatics·Jason A Vander HeidenSteven H Kleinstein
Aug 8, 2014·Science Translational Medicine·Joel N H SternKevin C O'Connor
Jun 13, 2015·Bioinformatics·Namita T GuptaSteven H Kleinstein
Jan 20, 2017·Nature Reviews. Disease Primers·Thomas J KippsKanti Rai
Oct 30, 2018·Nucleic Acids Research·John G TateSimon A Forbes
Apr 2, 2020·Cold Spring Harbor Perspectives in Medicine·Nicholas ChiorazziKanti R Rai

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