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


CONCLUSIONS
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.
Caligaris-Cappio
F
F
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Ospedale Mauriziano Umberto I, Italy. fcaligaris@mauriziano.it
Hamblin
T J
TJ
D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002869:Chromosome Aberrations; D016207:Cytokines / Q000502:physiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000503:physiopathology
D016207:Cytokines