title: Rapamycin provides a therapeutic option through inhibition of mTOR signaling             in chronic myelogenous leukemia.
abstract: Chronic myelogenous leukemia (CML) is a neoplasm of myeloid progenitor cells             expressing Bcr-Abl fusion protein. However, some patients with CML are less likely             to respond to imatinib, the inhibitor of Bcr-Abl kinase. Recent studies showed             that mTOR pathway can increase responses to imatinib. The analysis of mTOR pathway             in CML may provide new insights into possible targets of novel therapies. Therefore,             we examined the expression of mTOR pathway molecules in bone marrow cells from             CML patients and effect of rapamycin on K562 cells in vitro. Western blot analysis             showed the visibly higher phosphorylation of mTOR (70.6%), 4E-BP1 (76.5%) and             p70S6K (73.5%) in bone marrow cells from CML patients. Moreover, treatment of             CML cell line (K562) with rapamycin resulted in a decrease of phosphorylation             of mTOR, 4E-BP1 and p70S6K. In vitro, the cell viability in groups with rapamycin             treatment displayed a significant decrease in a dose-dependent manner by MTT.             The data presented an increase of G0/G1 phase cells and decrease of S phase cells             after rapamycin treatment, and the decreased expression of cyclinD1, higher expression             of p21 at mRNA level was also detected in K562 with rapamycin. Treatment with             20 nmol/l or more rapamycin could increase apoptotic cells, decrease expression             of bcl-2 and activate caspase-3. In conclusion, the mTOR pathway might be involved             in chronic myelogenous leukemia. Inhibition of mTOR pathway could interfer with             cell proliferation and increase cell apoptosis in K562 cells. It suggested that             mTOR might be an important therapeutic target for myelogenous leukemia.
authors: Department of Hematology, the Second Hospital, Hebei Medical University, Shijiazhuang 050017, PR China.
authors: Jie
authors: J
authors: Li
authors: Liying
authors: L
authors: Xue
authors: Hongling
authors: H
authors: Hao
authors: Yuxiang
authors: Y
authors: Han
authors: Jingci
authors: J
authors: Yang
authors: Jianmin
authors: J
authors: Luo
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus