Differences in BCL-X(L) expression and STAT5 phosphorylation in chronic myeloid leukaemia patients.
Chronic 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.
Gutiérrez-Castellanos
Sergio
S
Laboratorio de Hematología Especial, Servicio de Hematología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, México, D.F., México. sergutica@yahoo.com.mx
Cruz
Miguel
M
Rabelo
Laura
L
Godínez
Rocio
R
Reyes-Maldonado
Elba
E
Riebeling-Navarro
Carlos
C
D000328:Adult; D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D020014:K562 Cells / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D015465:Leukemia, Myeloid, Accelerated Phase / Q000235:genetics / Q000378:metabolism; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D051020:bcl-X Protein; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl