B-cell chronic lymphocytic leukemia: a bird of a different feather - PubMed (original) (raw)

Review

B-cell chronic lymphocytic leukemia: a bird of a different feather

F Caligaris-Cappio et al. J Clin Oncol. 1999 Jan.

Abstract

Purpose: To review the recent major advances in the molecular and cell biology of B-cell chronic lymphocytic leukemia (B-CLL).

Methods: We analyzed the nature of malignant B-CLL B cells and their interactions with the microenvironment.

Results: B-CLL is a malignancy of a mantle zone-based subpopulation of anergic, self-reactive, activated CD5+ B cells devoted to the production of polyreactive natural autoantibodies. It is the quintessential example of a human malignancy that primarily involves defects in the induction of programmed cell death. An abnormal karyotype is observed in about 50% of patients with B-CLL. Patients with 13q14 abnormalities show heavy somatic mutation and have a benign disease. Trisomy 12 is associated with unmutated VH genes, atypical cellular morphology, and progressive disease. Extended cell survival is further shielded by a kinetic refractoriness likely promoted by abnormalities of the B-cell antigen receptor complex and favored by some cytokines that highlight a reciprocal dialog between malignant B and T cells. Because the tumor cells act as the major accessory cells, the accumulating malignant B-cell population per se is a hurdle to the production of normal antibodies and leads to a progressive and severe hypogammaglobulinemia. Conceivably, in the presence of certain immunoglobulin genes and when the T-cell control becomes deficient, activated malignant B cells may become able to present self-antigens and drive residual normal B cells to produce polyclonal autoantibodies restricted to self-antigens expressed only by blood cells and cause autoimmune cytopenias.

Conclusion: The distinctiveness of B-CLL B cells explains why B-CLL is different from other B-cell tumors and accounts for the development of immune deficiency and autoimmunity.

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