A Dual Origin for Bcr-Abl Gene Translocation/Fusion as Dynamics of Synergism of the Hematopoietic Stem Cell and Hemangioblast in Chronic Myeloid Leukemia

Contextual BCR-ABL tyrosine kinase over-activity determines in formulated fashion the emergence of proliferation and anti-apoptosis that arise largely as derived phenomena of otherwise homeostatic mechanisms of the c-ABL gene within hematopoietic stem cells and hemangioblasts in the bone marrow. The ability to suppress almost completely, both in terms of phenotype and cytogenetically, the myeloid cell line expansion by imatinib mesylate is indicative of a phenomenon that depends strictly on the transformed status of the cell of origin in the chronic myeloid leukemia process. It is with relevance to complex participation of the dynamics of the fused BCRABL protein product that contextual conditioning of the cells of origin of the gene translocation further motivates the dimensional expansion of the transformed myeloid cell clones to increasing proliferative rates, thus leading to blast crisis as eventual loss of differentiating potential.