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The anti‐apoptotic genes Bcl‐X L and Bcl‐2 are over‐expressed and contribute to chemoresistance of non‐proliferating leukaemic CD34 + cells
Author(s) -
Konopleva Marina,
Zhao Shourong,
Hu Wei,
Jiang Shuwei,
Snell Virginia,
Weidner Douglas,
Jackson C. Ellen,
Zhang Xin,
Champlin Richard,
Estey Elihu,
Reed John C.,
Andreeff Michael
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03637.x
Subject(s) - cd34 , cell cycle , biology , apoptosis , cancer research , progenitor cell , microbiology and biotechnology , myeloid , retinoic acid , stem cell , gene , genetics
Summary. In acute myeloid leukaemia (AML), cell kinetic quiescence has been postulated to contribute to drug resistance. As the anti‐apoptotic genes Bcl‐2 and Bcl‐X L have been implicated in cell cycle regulation, we investigated the expression of these genes in non‐proliferating (Q) and proliferating (P) AML and normal CD34 + progenitor cells. Using reverse transcription polymerase chain reaction, Bcl‐X L and Bcl‐2 were overexpressed in Q versus P AML cells, whereas no difference in Bcl‐X S and Bax expression was found. Furthermore, the Bcl‐X L /X S but not the Bcl‐2/Bax ratio was higher in Q AML compared with normal CD34 + Q cells ( P = 0·001). An inverse correlation between Bcl‐2 expression of leukaemic Q cells and their ability to enter the cell cycle was found. Treatment with all‐ trans retinoic acid (ATRA) reduced Bcl‐2 and Bcl‐X L expression in the leukaemic Q cells, and enhanced their chemosensitivity to cytosine arabinoside (ara‐C). These findings demonstrate overexpression of the anti‐apoptotic proteins Bcl‐X L and Bcl‐2 in quiescent CD34 + AML cells and suggest their involvement in the chemoresistance. The observed inverse correlation between Bcl‐2 and proliferation suggests a role for Bcl‐2 in the cell cycle regulation of AML. These findings could be used in the development of therapies that selectively induce apoptosis in quiescent leukaemic progenitor cells.