Robert H. Lurie Comprehensive Cancer Center and Division of Hematology/Oncology, Northwestern University Medical School and Jesse Brown VA Medical Center, Chicago, IL, USA.
Leuk Lymphoma. 2011 Feb;52 Suppl 1:45-53. doi: 10.3109/10428194.2010.546919.
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.
大量证据表明，BCR-ABL 调节哺乳动物雷帕霉素靶蛋白（mTOR）和丝裂原活化蛋白激酶（MAPK）信号级联的募集和激活。mTOR 介导的信号以及 ERK、JNK 和 p38 MAPK 转导的信号是 BCR-ABL 诱导的异常信号的重要组成部分。mTOR 或 MAPK 途径的这种失调导致 BCR-ABL 白血病的发生，并且使用选择性抑制剂靶向这些途径为增强抗白血病反应和/或克服慢性髓性白血病（CML）和费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）中的白血病细胞耐药性提供了一种方法。本综述探讨了我们对 BCR-ABL 表达白血病中 mTOR 和 MAPK 信号的理解的最新进展，并讨论了这些途径在 CML 和 Ph+ ALL 中的潜在治疗靶向。
