The Role of the STAT5 Proteins in the Proliferation and Apoptosis of the CML and AML Cells

Objectives: The STAT5 proteins are activated by many haematological cytokines and growth factors. They regulate cell cycle, apoptosis and proliferation of different cells via the influence on gene transcription. Because STAT5s are constitutively activated in certain haematooncologic diseases, they are suggested to play an important role in leukaemogenesis. However, the real function of these proteins in haematopoietic cell transformation and proliferation is not clear enough. The aim of this study was to evaluate the influence of suppression of STAT5A and STAT5B expression on the clonogenicity and apoptosis of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells.

Material And Methods: Blast cells from 34 newly diagnosed patients with CML and AML were used in our experiments. Antisense oligodeoxynucleotides (ODNs) were applied to block STAT5A and STAT5B at the mRNA level and the RT-PCR method was used to study STAT5 mRNA expression in the cells after incubation with ODNs. Moreover, Western blot analysis of the STAT5 proteins was performed. The effect of ODN pretreatment on cell clonogenicity in methylocellulose cultures was examined according to the type of oligodeoxynucleotide and the time of exposure. The induction of apoptosis in cells was also estimated by the Annexin V/PI staining and the TUNEL method using flow cytometry.

Results: Perturbation of STAT5 expression decreased proliferative potential of the CML and the AML blasts as well as enhanced their apoptosis (P < 0.05).

Conclusions: Our studies showed that the STAT5 proteins may be critical in the regulation of growth and apoptosis of the CML and AML leukaemic cells.