• Sergio Gutiérrez-Castellanos, Miguel Cruz, Laura Rabelo, Rocio Godínez, Elba Reyes-Maldonado, and Carlos Riebeling-Navarro.
• Laboratorio de Hematología Especial, Servicio de Hematología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, México, D.F., México. sergutica@yahoo.com.mx
• Eur. J. Haematol. 2004 Apr 1; 72 (4): 231-8.

AbstractChronic myelogenous leukaemia (CML) cells show expression of BCL-X(L), an anti-apoptotic oncogene. This expression is induced by BCR-ABL protein kinase through activation of the signal transducer and activator of transcription-5 protein (STAT5). To date, however, the contribution of BCL-X(L) and STAT5 to the transforming phenotype in CML is still unclear. This study was aimed at defining the status of activated STAT5 and BCL-X(L) expression and their relation to BCR-ABL rearrangement in CML cells derived from patients at different clinical stages. Twenty-seven consecutive patients with CML were enrolled in the study. Peripheral blood mononuclear cells were lysed and subjected to immunoprecipitation and Western blotting to analyse phosphorylated STAT5. The p210 BCR-ABL rearrangements were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and BCL-X(L) expression by semi-quantitative RT-PCR. We found that increased transcription of BCL-X(L) gene was associated with phosphorylated STAT5 in the majority of blast crisis patients and in a few accelerated and chronic phase patients. Moreover, BCL-X(L) expression levels were found to be decreased in chronic phase, contrary to a marked increase in blast crisis. We found no difference in expression of BCL-X(L) and phosphorylated STAT5 when related with b3a2 and b2a2 BCR-ABL rearrangements. These results suggest that STAT5 activity and BCL-X(L) overexpression may reflect a stage of differentiation among CML phases, and this could contribute to BCR-ABL-dependent transformation.

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