Differences in BCL-XL expression and STAT5 phosphorylation in chronic myeloid leukaemia patients
Eur J Haematol 2004: 72: 231–238. © Blackwell Munksgaard 2004. Abstract:
Chronic myelogenous leukaemia (CML) cells show expression of BCL-XL, 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-XL and STAT5 to the transforming phenotype in CML is still unclear. This study was aimed at defining the status of activated STAT5 and BCL-XL 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-XL expression by semi-quantitative RT-PCR. We found that increased transcription of BCL-XL gene was associated with phosphorylated STAT5 in the majority of blast crisis patients and in a few accelerated and chronic phase patients. Moreover, BCL-XL 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-XL and phosphorylated STAT5 when related with b3a2 and b2a2 BCR-ABL rearrangements. These results suggest that STAT5 activity and BCL-XL overexpression may reflect a stage of differentiation among CML phases, and this could contribute to BCR-ABL-dependent transformation.
Document Type: Research Article
Affiliations: 1: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades 2: Laboratorio de Hematología Especial, Servicio de Hematología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, México, D.F., México 3: Laboratorio de Citología, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, D.F., México 4: Servicio de Reumatología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, México, D.F., México
Publication date: April 1, 2004