Which has greater effects on leukomogenesis in Philadelphia chromosome positive leukemias: fusion or cell type? (Philadelphia kromozomu pozitif olan lösemilerde lökomogenez üzerinde hangisi daha etkilidir: Füzyon veya hücre tipi?)

Aim: The occurrence of different breakpoint cluster region/c-abl oncogene 1 (BCR-ABL) fusion forms in several types of Philadelphia chromosome positive leukemia suggests these proteins have alternative leukomogenic activity. Distinct types of leukemia diverge from each other with respect to levels of telomerase and telomere lengths. It is known that telomeres and telomerase are essential to the regulation of cell life-span and division. It has been hypothesized that the difference in leukomogenic activities of distinct forms of BCR-ABL fusion could be related to the telomere length and telomerase activity of the hematopoietic cells transformed by these proteins. Material and methods: We have compared the effects of p190BCR-ABL and p210BCR-ABL on telomerase activity, telomere length and proliferative rate of myeloid (32D cl3) and lymphoid (Ba/F3) cell lines transformed by both fusion forms. Telomerase activity, telomere length and cell proliferation capacity were measured by Telomerase Repeat Amplification Protocol (TRAP), Terminal Restriction Fragments (TRF) and mitotic index respectively. Results: In myeloid cells, a difference was found between the p190BCR-ABL and p210 BCR-ABL with regard to telomerase related proliferative behaviour. p210BCR-ABL, unlike p190 BCR-ABL, is associated with increased mitotic index in both cells’ origin. Conclusion: Our results suggest that the leukomogenic activities of BCR-ABL fusion proteins in myeloid cell might be related to the telomerase activity and telomere length of the cells. To realize intracellular dynamics associated with cell proliferation, other targets for BCR-ABL fussion protein and telomerase should be investigated.