Ph positive-leukemias

Introduction Ph-positive leukaemias are clonal disorders characterized by the Philadelphia (Ph) chromosome genetic abnormality, which arises from the reciprocal chromosomal translocation t(9;22) (q34;q11).1 This translocation fuses the genes encoding BCR and ABL, resulting in expression of the constitutively active protein tyrosine kinase, BCR-ABL. Depending on the precise translocation breakpoints and differential mRNA splicing, various molecular weight isoforms of BCR-ABL are generated. These isoforms are associated with distinct types of leukemia.2 Most (>90%) of patients with chronic myeloid leukaemia (CML) and one third of patients with Ph+ acute lymphocytic leukemia (ALL) express the 210-kDa oncoprotein. Twenty percent to 30% of cases of Ph+ ALL and a few cases of CML are associated with 185-kDa BCRABL. A subset of patients with indolent CML expresses the 230- kDa BCR-ABL oncoprotein. Differences in intrinsic kinase activity and cell context may influence the type of leukemia that arises with each BCR-ABL isoform and the development of therapeutic agents to treat these BCR-ABL–driven malignancies.3 Although imatinib has emerged as a very powerful drug, most of the patients who achieved responses are at risk of relapse because the leukaemic stem cell pool has not been eradicated.4 In this paper, we will review some data on the pathophysiology of the disease focusing mainly on stem cells.