Role of myeloid cell factor-1 (Mcl-1) in chronic lymphocytic leukemia

Leukemia & Lymphoma
James B JohnstonSpencer B Gibson

Abstract

The primary abnormality in chronic lymphocytic leukemia (CLL) is a defect in apoptosis, probably related to alterations in the expressions of Bcl-2 family members. In transgenic mice over expressing the anti-apoptotic Bcl-2 family member, myeloid cell factor-1 (Mcl-1), B cell lymphomas occur. Moreover, mice conditional for the loss of Mcl-1 display a profound reduction in B and T lymphocytes. This suggests that Mcl-1 is an essential survival factor in lymphocytes. In the present study, we have evaluated the role of Mcl-1 in CLL. Mcl-1 protein expression was measured by Western blot analysis in the CLL cells of 45 patients and correlated with clinical variables and survival. Mcl-1 levels were similar in 29 patients to normal B and T lymphocytes, were decreased in 8 patients and increased in 12 patients. An inverse correlation was found between Mcl-1 expression and Rai stage (P = 0.001). When assessed by flow cytometry, Mcl-1 expressions were normally distributed among CLL cells in individual patients and the mean levels correlated with those obtained by Western blotting. To evaluate the role of Mcl-1 in drug resistance, Mcl-1 levels were sequentially measured in the leukemic cells of 4 CLL patients during therapy with fludarabin...Continue Reading

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Citations

Jun 10, 2006·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·David HuiRaymond Lai
Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·George A CalinCarlo M Croce
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Jan 19, 2008·Leukemia & Lymphoma·Elizabeth S HensonSpencer B Gibson
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Aug 20, 2005·Leukemia & Lymphoma·James T PaulJames B Johnston
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Jul 19, 2020·Experimental Hematology·Stefania BottardiEric Milot

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