Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells.

作者: Sten Orrenius , David J. McConkey , Mikael Jondal , Håkan Mellstedt , Pia Hartzell

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摘要: Chronic lymphocytic leukemia of B cell type (B-CLL) is a neoplastic disorder characterized by the accumulation small resting lymphocytes in periphery. The phenotype these cells suggests that they are "frozen" at an early stage maturation. Glucocorticoid hormones commonly used to treat patients with B-CLL, resulting reduction peripheral lymphocyte count undefined mechanism. Here we report glucocorticoids stimulate DNA fragmentation characteristic suicide process known as apoptosis or programmed death (PCD) suspensions from B-CLL. effects can be mimicked Ca2+ ionophore and involve sustained increase cytosolic concentration. Specific antibodies binding membrane-associated IgM on leukemic also induce PCD similar Phorbol esters block killing response all agents, suggesting activation protein kinase C desensitizes PCD. Targeting B-CLL unbalanced, may therefore represent rational strategy for destruction cells.

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