PMID- 22021366
OWN - NLM
STAT- MEDLINE
DCOM- 20120214
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 118
IP  - 24
DP  - 2011 Dec 8
TI  - Antileukemic effects of AMPK activators on BCR-ABL-expressing cells.
PG  - 6399-402
LID - 10.1182/blood-2011-01-332783 [doi]
AB  - The mammalian target of rapamycin (mTOR) signaling pathway plays a critical role 
      in growth and survival of BCR-ABL transformed cells. AMPK kinase is a metabolic 
      sensor that exhibits suppressive effects on the mTOR pathway and negatively 
      regulates mTOR activity. We report that AMPK activators, such as metformin and 
      5-aminoimidazole-4-carboxamide ribonucleotide, suppress activation of the mTOR 
      pathway in BCR-ABL-expressing cells. Treatment with these inhibitors results in 
      potent suppression of chronic myeloid leukemia leukemic precursors and Ph(+) 
      acute lymphoblastic leukemia cells, including cells expressing the T315I-BCR-ABL 
      mutation. Altogether, our data suggest that AMPK is an attractive target for the 
      treatment of BCR-ABL-expressing malignancies and raise the potential for use of 
      AMPK activators in the treatment of refractory chronic myeloid leukemia and Ph(+) 
      acute lymphoblastic leukemia.
FAU - Vakana, Eliza
AU  - Vakana E
AD  - Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA.
FAU - Altman, Jessica K
AU  - Altman JK
FAU - Glaser, Heather
AU  - Glaser H
FAU - Donato, Nicholas J
AU  - Donato NJ
FAU - Platanias, Leonidas C
AU  - Platanias LC
LA  - eng
GR  - R01 CA121192/CA/NCI NIH HHS/United States
GR  - P30 CA060553/CA/NCI NIH HHS/United States
GR  - R01CA121192/CA/NCI NIH HHS/United States
GR  - R01CA77816/CA/NCI NIH HHS/United States
GR  - R01 CA077816/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111021
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Mutant Proteins)
RN  - 0 (Prodrugs)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Amino Acid Substitution
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Bone Marrow Cells/drug effects/metabolism
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects
MH  - Cell Transformation, Neoplastic/*metabolism
MH  - Down-Regulation/drug effects
MH  - Drug Resistance, Neoplasm
MH  - Enzyme Activation/drug effects
MH  - Fusion Proteins, bcr-abl/genetics/*metabolism
MH  - Hematopoietic Stem Cells/drug effects/metabolism
MH  - Humans
MH  - Leukemia, Lymphoid/drug therapy/metabolism
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/drug therapy/metabolism
MH  - Metformin/pharmacology
MH  - Molecular Targeted Therapy
MH  - Mutant Proteins/metabolism
MH  - Prodrugs/pharmacology
MH  - Protein Kinases/*chemistry
MH  - Recombinant Proteins/metabolism
MH  - Ribonucleotides/pharmacology
PMC - PMC3236122
EDAT- 2011/10/25 06:00
MHDA- 2012/02/15 06:00
PMCR- 2012/12/08
CRDT- 2011/10/25 06:00
PHST- 2011/10/25 06:00 [entrez]
PHST- 2011/10/25 06:00 [pubmed]
PHST- 2012/02/15 06:00 [medline]
PHST- 2012/12/08 00:00 [pmc-release]
AID - S0006-4971(20)40508-7 [pii]
AID - 2011/332783 [pii]
AID - 10.1182/blood-2011-01-332783 [doi]
PST - ppublish
SO  - Blood. 2011 Dec 8;118(24):6399-402. doi: 10.1182/blood-2011-01-332783. Epub 2011 
      Oct 21.