Treatment of Philadelphia positive (Ph+)ALL and CML in children

Philadelphia positive (Ph+) leukemias in children include essentially all chronic myeloid leukemias (CML) and 2% to 3% of childhood acute lymphoblastic leukemias (ALLs). Ph+ leukemias are characterized by a reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome). The translocation creates a fusion of human homologue of the Abelson Murine leukemia virus ABL on chromosome 9q34, with breakpoint cluster region BCR on 22q11 (reviewed in ref. 1) An in frame BCR-ABL fusion transcript results in the upregulation of the abl tyrosine kinase. Primarily, three main BCR-ABL chimeric transcripts arise from distinct breakpoints in the BCR gene, resulting in fusion of the BCR exon 1, exon 1-12/13 or exons 1-19 to ABL. The molecular masses of the protein products are 185/190, 210 and 230 kDa respectively. In most patients with CML and in approximately 10% of patients of ALL it is the p210BCR-ABL product which is produced, although low levels of the p185BCR-ABL product are often detect in CML patients. For the majority of Ph+ALL and in occasional patients with CML, a p185BCR-ABL product is found. The alternative translocation product, ABL-BCR can be detected but is not thought to play a role in leukemogenesis (1).