| Summary: | The chronic myeloid leukemia (CML) is the three-phasemyeloproliferative disorder, dependent on the expression of theoncoprotein Bcr-Abl, which is the product of the reciprocaltranslocation between chromosomes 9 and 22, resulting in thePhiladelphia chromosome (Ph). Bcr-Abl protein is the constitutivelyactivated tyrosine kinase responsible for changes in intracellularbiochemical cascades, culminating into hematopoieticic stem cellmalignant transformation. CML leukemic cells present abnormaladhesion to medullar stroma, altered proliferation and an amazingresistance to apoptosis induced by classical chemotherapeuticdrugs. Another therapy used in CML patients is imatinib mesylate(Gleevecâ), which has shown remarkable clinical activity in thesepatients. However, this drug does not completely eradicate BCRABL-expressing cells from the body, and recently some patientsshowed resistance to imatinib. The observation that production ofBcr-Abl is the initiating event in CML drew attention to the survivalsignals triggered by this oncogene. The number of altered signaltransducers and transcription factors has been associated withthe anti-apoptotic phenotype of CML cells, and some of them leadto the expression and/or activation of apoptosis modulators fromBcl-2 family, such as Bcl-xL, Bcl-2, Bax and Bad. In this article wereview some recent data on the understanding of Bcr-Abloncoprotein expression effect in the apoptosis machinery in CML.
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