Survival of leukemic B cells promoted by engagement of the antigen receptor.

TitleSurvival of leukemic B cells promoted by engagement of the antigen receptor.
Publication TypeJournal Article
Year of Publication2001
AuthorsBernal A, Pastore RD, Asgary Z, Keller SA, Cesarman E, Liou HC, Schattner EJ
Date Published2001 Nov 15
KeywordsAged, Aged, 80 and over, Apoptosis, B-Lymphocytes, bcl-X Protein, Blotting, Western, CD40 Antigens, CD5 Antigens, Cell Survival, Electrophoretic Mobility Shift Assay, Female, Gene Expression Regulation, Leukemic, Humans, Immunoglobulin M, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Microscopy, Fluorescence, Middle Aged, Minor Histocompatibility Antigens, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Neoplastic Stem Cells, NF-kappa B, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-bcl-2, Receptors, Antigen, B-Cell, RNA, Messenger, RNA, Neoplasm

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-kappaB, 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.

Alternate JournalBlood
PubMed ID11698290
Grant ListCA-68155 / CA / NCI NIH HHS / United States
CA-71589 / CA / NCI NIH HHS / United States
Related Faculty: 
Ethel Cesarman, M.D., Ph.D.

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