The role of RAS effectors in BCR/ABL induced chronic myelogenous leukemia
The role of RAS effectors in BCR/ABL induced chronic myelogenous leukemia
Jessica Fredericks, Ruibao Ren()
State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA
BCR/ABL is the causative agent of chronic myelogenous leukemia (CML). Through structure/function analysis, several protein motifs have been determined to be important for the development of leukemogenesis. Tyrosine177 of BCR is a Grb2 binding site required for BCR/ABL-induced CML in mice. In the current study, we use a mouse bone marrow transduction/transplantation system to demonstrate that addition of oncogenic NRAS (NRASG12D) to a vector containing a BCR/ABLY177F mutant “rescues” the CML phenotype rapidly and efficiently. To further narrow down the pathways downstream of RAS that are responsible for this rescue effect, we utilize well-characterized RAS effector loop mutants and determine that the RAL pathway is important for rapid induction of CML. Inhibition of this pathway by a dominant negative RAL is capable of delaying disease progression. Results from the present study support the notion of RAL inhibition as a potential therapy for BCR/ABL-induced CML.
. The role of RAS effectors in BCR/ABL induced chronic myelogenous leukemia[J]. Frontiers of Medicine, 2013, 7(4): 452-461.
Jessica Fredericks, Ruibao Ren. The role of RAS effectors in BCR/ABL induced chronic myelogenous leukemia. Front Med, 2013, 7(4): 452-461.
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