Targeted therapy for chronic myelogenous leukemia (CML). (a) One of the more common molecular changes in hematopoietic cells from CML patients is a reciprocal translocation (swap) of DNA between the long arms of chromosomes 9 and 22. This translocation forms the 'fusion' gene BCR-ABL, which encodes a constitutively active ABL kinase. (b) The constitutive activity of BCR-ABL in hematopoietic CML cells drives several candidate oncogenic signaling pathways. Hematopoietic cells in CML patients are 'addicted' to BCR-ABL signaling such that BCR-ABL inhibition impairs their viability. (c) Tyrosine kinases such as ABL and BCR-ABL have well defined catalytic domains that bind ATP and use its phosphate moiety to post-translationally modify substrate proteins. Drugs such as imatinib bind and block the catalytic domain and in doing so limit hematopoietic cell proliferation in CML patients. (b) and (c) modified from  and .