Similar patterns of Vα gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, waldenstrom's macroglobulinemia, and myeloma

Abstract

To compare Vκ gene usage and the amount of somatic mutation in rearranged Ig genes from patients with lymphoproliferative disorders, we have polymerase chain reaction-amplified and sequenced a total of 26 Vκ genes from a total of 55 cases. Six sequences were obtained both from six cases of prolymphocytic leukemia (PLL) and from nine cases of hairy cell leukemia (HCL). Seven sequences were obtained both from 11 cases of Waldenström's macroglobulinemia (WM) and 29 cases of multiple myeloma (MM). Eleven different germline genes have been used in this series, indicating a wide but nonrandom usage of germline Ig gene rearrangements in these disorders. Comparison of the nucleotide sequences of Vκ genes obtained from B-cell malignancies with germline Vκ genes shows that somatic mutation is rare in PLL and HCL and common in WM and MM. Analysis of the pattern of mutations suggests that WM and MM are derived from B cells that have been selected by antigen at a relatively late stage of differentiation. © 1994 by The American Society of Hematology.