Philadelphia-positive B-cell acute lymphoblastic leukemia is initiated in an uncommitted progenitor cell

BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-ABLgene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, BCR-ABLp190 and BCR-ABLp210, are produced that are characteristic of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (Ph1-ALL) respectively. In CML, it is evident that the transformation occurs at the level of pluripotent stem cells. However, Ph1-ALL has been thought to affect progenitor cells with lymphoid differentiation. Recently, it has been demonstrated that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation in Ph1-ALL. In this review, we discuss what is known about the relationship between the specific BCR-ABLp190 oncogene, the target cell and the characteristics of the subsequent disease process it causes. We also discuss how this information may be applied to the establishment of new directions in therapy.