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. Alternat ive chimeric proteins, BCR-ABLp(190) and BCR-ABLp(210), are produced that a re characteristic of chronic myelogenous leukemia (CML) and acute lymphobla stic leukemia (Ph-1-ALL) respectively. In CML, it is evident that the trans formation occurs at the level of pluripotent stem cells. However, Ph-1-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 Ph-1-ALL. In this review, we discuss what is known about the relationship b etween the specific BCR-ABLp(190) oncogene, the target cell and the charact eristics of the subsequent disease process it causes. We also discuss how t his information may be applied to the establishment of new directions in th erapy.