BCR-ABL and Human Cancer

摘要: The BCR-ABL oncogene was the first chromosomal abnormality shown to be associated with a specific human malignancy, chronic myelogenous leukemia (CML), resulting from reciprocal t(9;22) translocation characterized by formation of shortened chromosome, named Philadelphia chromosome (Ph), in which tyrosine kinase c-ABL is constitutively activated. This generates fusion genes can translated three different oncoproteins, p210, p190, and p230, pathologies humans, CML, acute lymphoblastic (ALL), neutrophilic leukemia, respectively. molecular mechanisms downstream pathways are poorly understood mainly as result lack good vivo model that mimics disease. Nevertheless, additional vitro models have led design several novel therapeutic approaches. That case Imatinib mesylate (Gleevec, STI571; Novartis Pharma AG), drug targeting activity an effective therapy for phase CML but not advanced stages patients Ph+ ALL. resistance mutations domain together stem cell origin inability imatinib inhibit these cells revealed limitations Gleevec, providing new lessons development alternative therapies oncology.