BACKGROUND: The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is 
the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that 
BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the 
regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at 
multiple levels in K562 cells.
METHODS: Molecular techniques such as over expression, knockdown, real-time PCR, 
immunoprecipitation, western blotting, reporter assay, confocal microscopy, 
telomerase assays and microarray were used to suggest that hTERT expression and 
activity is modulated by BCR-ABL at multiple levels.
RESULTS: Our results suggest that BCR-ABL plays an important role in regulating 
hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited 
the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was 
downregulated, therefore suggesting a positive correlation between BCR-ABL and 
hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced 
telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL 
negative cells). We also demonstrated that the transcription factor STAT5a plays 
a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but 
not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and 
hTERT protein level in K562 cells. Furthermore, translocation of hTERT from 
nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec.
CONCLUSIONS: Our data reveal that BCR-ABL can regulate TA at multiple levels, 
including transcription, post-translational level, and proper localization. 
Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment 
may be partially due to TA inhibition. Additionally, we have identified STAT5a 
as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, 
suggesting that targeting STAT5a may be a promising therapeutic strategy for 
BCR-ABL positive CML patients.