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

Abstract

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.