The origin of B-cell chronic lymphocytic leukemia

Seminars in Oncology
Paolo Ghia, Federico Caligaris-Cappio

Abstract

An immunobiologic approach has led to substantial changes in our current view of chronic lymphocytic leukemia (CLL). Several questions remain unsolved and the definition of the cell origin of CLL is still prominent. The presence of somatic mutations of IGHV genes indicates that, at least in a portion of cases, CLL cells had encountered an antigen during the natural history of the disease. Unmutated (UM) cases show a remarkable skewing in IGHV gene usage. In addition, all CLL cases, both mutated (M) and UM, show a common surface phenotype which is significantly activated and similar to the surface phenotype of antigen (Ag)-experienced B cells. The properties of CLL B-cell receptors (BCR) resemble those observed in normal B cells upon Ag interaction, and gene profiling analyses revealed that both subsets share striking similarities with the so-called memory B cells. The detailed analyses of the complementary determining region 3 (CDR3) sequences of the leukemic immunoglobulin (Ig) receptors showed that unrelated patients in different parts of the world express very similar if not identical BCR. Remarkably, similar V(H)DJ(H) rearrangements have been identified in both UM- and M-CLL, suggesting an antigenic selection in both subset...Continue Reading

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