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Blood, 15 November 2001, Vol. 98, No. 10, pp. 3050-3057
NEOPLASIA
Survival of leukemic B cells promoted by engagement of the
antigen receptor
Alejandro Bernal,
Raymond
D. Pastore,
Zahra Asgary,
Shannon A. Keller,
Ethel Cesarman,
Hsiou-Chi Liou, and
Elaine J. Schattner
From the Immunology Program, Weill Graduate School of
Medical Sciences of Cornell University, and Departments of Medicine and
Pathology, Weill Medical College of Cornell University, New York, NY.
Chronic lymphocytic leukemia (CLL) is an incurable leukemia
characterized by the slow but progressive accumulation of cells in a
CD5+ B-cell clone. Like the nonmalignant counterparts, B-1
cells, CLL cells often express surface immunoglobulin with the capacity to bind autologous structures. Previously there has been no established link between antigen-receptor binding and inhibition of apoptosis in
CLL. In this work, using primary CLL cells from untreated patients with
this disease, it is demonstrated that engagement of surface IgM
elicits a powerful survival program. The response includes inhibition of caspase activity, activation of NF- B, and expression of mcl-1, bcl-2, and bfl-1 in the tumor cells. Blocking
phosphatidylinositol 3-kinase (PI3-K), a critical mediator of signals
through the antigen receptor, completely abrogated mcl-1 induction and
impaired survival in the stimulated cells. These data support the
contention that CLL cell survival is promoted by antigen for
which the malignant clone has affinity, and suggest that pharmacologic
interference with antigen-receptor-derived signals has potential for
therapy in patients with CLL.
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