Evidence of canonical somatic hypermutation in hairy cell leukemia
- 5 May 2011
- journal article
- Published by American Society of Hematology in Blood
- Vol. 117 (18), 4844-4851
- https://doi.org/10.1182/blood-2010-11-316737
Abstract
To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition.Keywords
This publication has 46 references indexed in Scilit:
- Insight into the molecular pathogenesis of hairy cell leukaemia, hairy cell leukaemia variant and splenic marginal zone lymphoma, provided by the analysis of their IGH rearrangements and somatic hypermutation patternsBritish Journal of Haematology, 2010
- VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapyBlood, 2009
- Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behaviorBlood, 2009
- Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell LeukemiaJournal of Clinical Oncology, 2009
- Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemiaBritish Journal of Haematology, 2009
- Somatic Mutation of Human Immunoglobulin V Genes: Bias, Rate, and RegulationAnnals of the New York Academy of Sciences, 2008
- Evolution of Autoantibody Responses via Somatic Hypermutation Outside of Germinal CentersScience, 2002
- Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human V rearrangementsImmunological Reviews, 1998
- The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacementImmunology Today, 1994
- Evolutionary nucleotide replacements in DNANature, 1979