PMID- 24112092
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20211203
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 92
IP  - 2
DP  - 2014 Feb
TI  - Mammalian target of rapamycin inhibitor rapamycin enhances anti-leukemia effect 
      of imatinib on Ph+ acute lymphoblastic leukemia cells.
PG  - 111-20
LID - 10.1111/ejh.12202 [doi]
AB  - BCR-ABL fusion gene typically causes a type of acute lymphoblastic leukemia 
      (ALL), known as Ph+ ALL. Although imatinib (IM) treatment induced high rates of 
      complete response (CR), serious acute and late complications are frequent, 
      whereas more vexatiously resistance to chemotherapy and clinical relapse 
      develops. Therefore, the efficacy of treatment in Ph+ ALL is still to be 
      determined. In this study, we focused our attention on the potential benefit of 
      rapamycin (RAPA), an mammalian target of rapamycin (mTOR) inhibitor, in 
      combination with IM on a Ph+ ALL cell line SUP-B15 and a primary Ph+ ALL sample 
      in vitro. Analysis of cell proliferation showed that RAPA (50 nm) plus IM exerted 
      good synergistic effect on Ph+ ALL cells. Notably, we found that IM treatment 
      induced the abnormal activation of the components of mTOR signaling pathway and 
      p-BCR-ABL, whereas RAPA potently eliminated this deleterious side effect induced 
      by IM and might overcome the resistance to IM. The synergistic effect was also 
      associated with the increase in autophagy, which seemed to have an opposite role 
      with apoptosis in Ph+ ALL cells, and cell cycle arrest in G1 phase. Altogether, 
      our results suggested that IM in combination with RAPA was more effective for Ph+ 
      ALL cells than IM alone.
CI  - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Yang, Xi
AU  - Yang X
AD  - Department of Hematology and State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, China.
FAU - He, Guangcui
AU  - He G
FAU - Gong, Yuping
AU  - Gong Y
FAU - Zheng, Bohui
AU  - Zheng B
FAU - Shi, Fangfang
AU  - Shi F
FAU - Shi, Rui
AU  - Shi R
FAU - Yang, Xiaojing
AU  - Yang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140106
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Apoptosis/drug effects
MH  - Benzamides/*pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - G1 Phase Cell Cycle Checkpoints/drug effects
MH  - Humans
MH  - Imatinib Mesylate
MH  - Piperazines/*pharmacology/therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - Pyrimidines/*pharmacology/therapeutic use
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Ph+ acute lymphoblastic leukemia
OT  - autophagy
OT  - imatinib
OT  - mammalian target of rapamycin signaling pathway
OT  - rapamycin
EDAT- 2013/10/12 06:00
MHDA- 2014/10/29 06:00
CRDT- 2013/10/12 06:00
PHST- 2013/09/06 00:00 [accepted]
PHST- 2013/10/12 06:00 [entrez]
PHST- 2013/10/12 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
AID - 10.1111/ejh.12202 [doi]
PST - ppublish
SO  - Eur J Haematol. 2014 Feb;92(2):111-20. doi: 10.1111/ejh.12202. Epub 2014 Jan 6.