Abstract
BCR/ABL induced chronic myelogenous leukemia (CML) is a biphasic disease characterized by the expansion of myeloid lineage granulocytic cells during its chronic phase and the expansion of immature cells during the later blast crisis. In humans, progression into blast crisis is often observed with proliferation of immature myeloid cells, however in one third of the cases proliferation of immature lymphoid cells occur. The mechanism behind different lineage expansion is unknown. Mouse models are efficient in mimicking the chronic phases of the BCR/ABL induced CML and are used to investigate the factors altering the disease phenotype in order to provide the patients with more effective treatment strategies in future. Previous studies showed that different levels of BCR/ ABL expression or certain mutations within BCR/ ABL can alter the disease phenotype in mouse models. In the mouse model, BCR/ABL P185 causes a CML-like myeloproliferative disease. BCR/ABL P185 with the point mutation Y283F in its BCR region, however, causes a mixed disease with characteristics of CML and acute lymphoblastic leukemia. The mechanism behind this phenotypic difference has not been well defined. I studied the differences in transformation potentials of the BCR/ ABL oncogenes with or without the tyrosine 283. I showed that this tyrosine residue may be important in myeloid lineage transformation and may not be playing a role in lymphoid lineage transformation. Moreover, I revealed a decrease in activation of two signaling proteins, Stat5 and rpS6, in BCR/ABL Y283F compared to P185.