Consequences of BCR-ABL expression within the hematopoietic stem cell in chronic myeloid leukemia

Chronic myeloid leukemia (CML) was the first human malignancy shown to be associated with a specific cytogenetic lesion, the Philadelphia chromosomal translocation. Forty years on, many biological and biochemical properties have been ascribed to its molecular product, the BCR-ABL tyrosine kinase fusion protein. However, it has been difficult to establish their precise contribution to the deregulation of normal survival, proliferative and differentiative control in chronic phase CML and the degree to which the involvement of stem cells extends beyond their role as the aetiological target. This review will focus on our current understanding of the pathogenesis of CML from the perspective of stem cell involvement, and how the biological and biochemical properties ascribed to BCR-ABL from studies of in vitro transformation and in vivo leukemogenesis systems relate to the abnormalities manifest in the human disease.