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Chronic Lymphocytic Leukemia B Cells Are Resistant to the Apoptotic Effects of Transforming Growth Factor-β

1997; Elsevier BV; Volume: 89; Issue: 3 Linguagem: Inglês

10.1182/blood.v89.3.941

1528-0020

Raymond S. Douglas, Renold J. Capocasale, Roberta J. Lamb, Peter C. Nowell̀, Jonni S. Moore,

Pancreatic and Hepatic Oncology Research

Abstract Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western world and is characterized by a slowly progressing accumulation of clonal CD5+ B cells. Our laboratory has investigated the role of transforming growth factor-β (TGF-β) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion in CLL. In vitro addition of TGF-β did not increase spontaneous apoptosis of B cells from most CLL patients, as determined using the TUNEL method, compared with a twofold increase observed in cultures of normal B cells. There was similar expression of TGF-β type II receptors on both CLL B cells and normal B cells. In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with addition of TGF-β. In vitro addition of IL-4, previously reported to promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells compared with normal B cells. CLL B-cell expression of IL-4 receptors was increased compared to normal B cells. Thus, our results show aberrant apoptotic responses of CLL B cells to TGF-β and IL-4, perhaps contributing to the relative expansion of the neoplastic clone.