Regulation of mammalian target of rapamycin and mitogen activated protein kinase pathways by BCR-ABL

A large body of evidence has established that BCR--ABL regulates engagement and activation of mammalian target of rapamycin (mTOR) and mitogen activated protein kinase (MAPK) signaling cascades. mTOR-mediated signals, as well as signals transduced by ERK, JNK, and p38 MAPK, are important components of the aberrant signaling induced by BCR--ABL. Such deregulation of mTOR or MAPK pathways contributes to BCR--ABL leukemogenesis, and their targeting with selective inhibitors provides an approach to enhance antileukemic responses and/or overcome leukemic cell resistance in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph++) acute lymphoblastic leukemia (ALL). This review explores recent advances in our understanding of mTOR and MAPK signaling in BCR--ABL-expressing leukemias and discusses the potential therapeutic targeting of these pathways in CML and Ph++ ALL.