PMID- 16488473
OWN - NLM
STAT- MEDLINE
DCOM- 20070927
LR  - 20071203
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 30
IP  - 8
DP  - 2006 Aug
TI  - Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute 
      leukemia.
PG  - 1027-36
AB  - Phosphatidic acid (PA) is an important component of mammalian target of rapamycin 
      (mTOR) signaling and in the recruitment of Raf to the cell membrane. PA can be 
      produced by several mechanisms, including by a series of lysophosphatidic acid 
      acyl transferases (LPAATs). LPAAT-beta is an isoform that is overexpressed in 
      some human cancers and its inhibition has been investigated as a potential 
      targeted cancer therapy. We report that LPAAT-protein and enzyme activity in 
      acute leukemia cell lines and blasts from patient samples are equivalent to 
      levels in normal mononuclear cells. Treatment with the LPAAT-beta inhibitor 
      CT-32228 (Cell Therapeutics, Seattle, WA) uniformly induces apoptosis in multiple 
      leukemia cell lines. In patient samples, however, apoptosis was variably induced 
      by CT-32228 and appeared to be related to the degree of cellular proliferation. 
      The growth inhibitory effect of CT-32228 on normal hematopoietic progenitors was 
      more pronounced in cells induced to proliferate by growth factors. These data 
      suggest that CT-32228 may have potential in the treatment of acute leukemias, but 
      that efficacy is more directly related to the degree of cell proliferation rather 
      than to the level of LPAAT-beta expression or activity.
FAU - Douvas, Michael G
AU  - Douvas MG
AD  - Department of Pediatrics, Lineberger Comprehensive Cancer Center, University of 
      North Carolina at Chapel Hill School of Medicine, USA. mgd9a@virginia.edu
FAU - Hogan, Karen N
AU  - Hogan KN
FAU - Ji, YanShan
AU  - Ji Y
FAU - Hollenback, David
AU  - Hollenback D
FAU - Bonham, Lynn
AU  - Bonham L
FAU - Singer, Jack W
AU  - Singer JW
FAU - Mitchell, Beverly S
AU  - Mitchell BS
LA  - eng
GR  - R01-CA064192/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060220
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (CT-32228)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydrocarbons, Halogenated)
RN  - 0 (Triazines)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.52 (2-acylglycerophosphate acyltransferase)
SB  - IM
MH  - Acute Disease
MH  - Acyltransferases/*antagonists & inhibitors
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - HL-60 Cells
MH  - Humans
MH  - Hydrocarbons, Halogenated/*pharmacology
MH  - Leukemia/*drug therapy/*enzymology
MH  - Structure-Activity Relationship
MH  - Triazines/*pharmacology
EDAT- 2006/02/21 09:00
MHDA- 2007/09/28 09:00
CRDT- 2006/02/21 09:00
PHST- 2005/09/19 00:00 [received]
PHST- 2005/11/22 00:00 [revised]
PHST- 2005/11/23 00:00 [accepted]
PHST- 2006/02/21 09:00 [pubmed]
PHST- 2007/09/28 09:00 [medline]
PHST- 2006/02/21 09:00 [entrez]
AID - S0145-2126(05)00444-3 [pii]
AID - 10.1016/j.leukres.2005.11.018 [doi]
PST - ppublish
SO  - Leuk Res. 2006 Aug;30(8):1027-36. doi: 10.1016/j.leukres.2005.11.018. Epub 2006 
      Feb 20.