BCR/ABL transcripts and leukemia phenotype: an unsolved puzzle

The Philadelphia chromosome, arising as a consequence of the t(9;22) translocation, is one of the most frequent and certainly the most known cytogenetic abnormality present in human hematological malignancies. Unlike the vast majority of the other translocations, its presence is not restricted to a specific leukemia phenotype, but is found associated with chronic myelogenous leukemia as well as with a large percentage of acute lymphoblastic leukemias, particularly in elderly patients. Although its molecular counterpart is always represented by a rearrangement between the BCR and the ABL genes, this shows a certain degree of molecular variability. The pathogenetic relationship with the different leukemia phenotypes which have been found to be associated still awaits to be fully elucidated. However, a number of old and more recent observations seem to suggest that not only qualitative differences in the type of BCR/ABL proteins expressed, but also quantitative variations in their total level within the cells may have an important role in determining the leukemia phenotype.