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VOL. 72 (1), 27-36, 2006 ANTIAPOPTOTIC PROTEINS BCL2 AND BCLX...

reciprocal translocation between chromosomes 9 and 22 (4). Bcr-Abl
is believed to be the major responsible for CML pathogenesis as it is
able to transform hematopoietic cells and to induce myeloproliferative
disease in mice after bone marrow repopulation with Bcr-Abl-
expressing cells. The transformation pathways induced by Bcr-Abl are
not fully understood, but it seems clear that apoptosis protection is a
major mechanism by which Bcr-Abl allows the expansion of the
leukemic clon (5, 6).

Although the outcome of CML in blast crisis is fatal, the disease
can be cured by allogenic bone marrow transplantation during
chronic phase. Interferon-a (IFNa) has been used in CML treatment,
and in those patients where IFNa treatment failed, the treatment was
based on hydroxyurea or busulfan (7). More recently, a new drug,
imatinib (formerly STI571, trade name «Gleevec», or «Glivec»), was
introduced in CML treatment. Imatinib is a potent inhibitor of the
tyrosine kinase activity of Bcr-Abl and it is rapidly displacing other
treatments for CML (8). Imatinib is active in vitro on CML-derived
cells, and it has been proposed that imatinib mechanism of action
involves the apoptosis that follows Bcr-Abl inhibition (5, 6, 8).

In the present work we study the effect of Bcl2 and BclX
overexpression on the response to imatinib of a CML-derived cell line.
Our data indicate that both proteins inhibit the imatinib-mediated
apoptosis but imatinib still impairs cell growth. Thus, imatinib acts
through apoptosis-dependent and apoptosis-independent pathways.
The results suggests that the action of imatinib as anti-CML drug in
vivo may depend more on its cytostatic effects than on its apoptotic
effects.

MATERIAL AND METHODS

Cell culture and drugs

K562 cell line was obtained from the American Type Culture
Collection. Kbcl2v cells are K562 infected with a Bcl-2 retrovirus and
expressing high levels of Bcl-2 protein. K562-BclXL (KbclX) are cells
transfected with Bcl-XL (9). All cell lines were grown in RPMI 1640

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