TEL-fusion oncogenic tyrosine kinases determine leukemic cells response to idarubicin.
The family of BCR/ABL-related fusion tyrosine kinases (FTKs) is reported to participate in drug resistance in leukemogenesis. Our recent studies revealed a novel potential mechanism of resistance in FTK+ cells underlined by the stimulation of DNA repair. In this work we examined a role of TEL family fusion oncoproteins in the response to idarubicin. We used murine pro-B lymphoid cell line BaF3, and its TEL/ABL, TEL/JAK2 and TEL/PDGFbetaR-transformed clones. The transformed cells, in contrast to their non-transformed counterparts, exhibited resistance to idarubicin in the range 0.01-1 microM. The drug at 0.3 and 1 microM induced DNA damage in the form of strand breaks or/and alkali-labile sites in both transformed and control cells as evaluated by the alkaline Comet assay. The transformed cells removed the damage within 60 min, while the control cells required 120 min to recover. The results obtained suggest that TEL-related FTKs may stimulate the repair of DNA damaged by idarubicin and be relevant to the resistance of the leukemic cells to this drug.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl; D015255:Idarubicin / Q000494:pharmacology*; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000097764:ETS Translocation Variant 6 Protein; D053614:Janus Kinase 2
D000903:Antibiotics, Antineoplastic; D016044:Fusion Proteins, bcr-abl; D015255:Idarubicin; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; C491568:TEL-JAK2 fusion protein, mouse; C120888:TEL-PDGFRbeta fusion protein, human