| Autor: |
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 |
| Předmět: |
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| Zdroj: |
British Journal of Haematology; Aug2002, Vol. 118 Issue 2, p521-534, 14p |
| Abstrakt: |
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-XL 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-XL and Bcl-2 were overexpressed in Q versus P AML cells, whereas no difference in Bcl-XS and Bax expression was found. Furthermore, the Bcl-XL /XS 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-XL 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-XL 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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