Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia.

Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Research Abstract Details 

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Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Abstract Text:

Michael G Douvas,Karen N Hogan,YanShan Ji,David Hollenback,Lynn Bonham,Jack W Singer,Beverly S Mitchell,

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.

Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Publishing Authors By Initials

MG Douvas,KN Hogan,Y Ji,D Hollenback,L Bonham,JW Singer,BS Mitchell,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research

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Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Leukemia research

VOLUME: 30

Page Numbers: 1027-36

Journal Abbreviation: Leuk. Res.

ISSN: 0145-2126

DAY: 20

MONTH: 02

YEAR: 2006

Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7706787

Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Keywords Mesh Terms:

KEYWORDS: Triazines

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Information

Substance Name: 2-acylglycerophosphate acyltransferase

Registry Number: EC 2.3.1.52

Grant and Affiliation Information for Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia.

AFFILIATION: Department of Pediatrics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, USA. mgd9a@virginia.edu

Country: England

AGENCY: United States NCI

GRANT: R01-CA064192

ACRONYM: CA

MEDLINETA: Leuk Res

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