Genetics of the Immune System | Antigen Processing & Recognition | Leukocyte Development | Leukocyte Signaling & Gene Expression | Leukemia & Proliferative Disorders of Hematic Cells
Analysis of somatic hypermutations in IGHV genes from hairy cell leukemia immunoglobulin heavy chain rearrangements
American Association for Cancer Research Annual Meeting 2011, 2 - 6 Apr 2011, 348
B-cell receptors of malignant B-cells each contain a monoclonal immunoglobulin sequence which may be relevant for both prognosis and cell of origin. The character of somatic hypermutations (SHM) has been studied to predict whether antigen contacted the B-cell prior to its malignant transformation, or at least whether the SHMs observed are ‘canonical’ or consistent with those expected from mutation machinery used for antigen-driven SHM.
Hairy cell leukemia B-cell receptors have previously been evaluated for gene usage and homology to germline sequence, but detection of canonical SHMs have not been previously possible.
We examined SHM features in hairy cell leukemia (HCL) in a series of 130 immunoglobulin heavy chain gene (IgH) rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients.
Our results show that HCLc rearrangements exhibited canonical SHM similar to CLL and normal B-cells, and significantly more than HCLv rearrangements. This suggests that malignant cells from HCLc patients may have recognized antigen prior to malignant transformation, and that in some HCLv patients the malignant cells may originate by a different pathway.
No relevant conflicts of interest declared.
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