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Title: Transcription profiling by array of human acute myeloid leukemia to study ATX expression      
dateReleased:
05-10-2013
description:
Autotaxin (ATX) has been reported to act as a motility and growth factor in a variety of cancer cells. The ATX protein acts as a secreted lysophospholipase D (lysoPLD) by converting lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which signals via G-protein coupled receptors and has important functions in cell migration and proliferation. The current study demonstrates that ATX expression is upregulated and functionally active in FLT3-ITD+ human blasts. ATX expression was also found in normal human CD34+ progenitor cells and selected myeloid and lymphoid subpopulations. Stable transduction of mutant FLT3-ITD increased ATX mRNA in selected cell lines, whereas inhibition of FLT3-ITD signaling by sublethal doses of PKC412 led to a significant down-regulation of ATX. Moreover, results indicate that the Jun N-terminal kinase (JNK) is an important mediator between FLT3 signaling and ATX. In the presence of LPC, ATX expression led to a significant increase of proliferation. LPA caused proliferation of all tested cell lines, regardless of ATX expression and induced chemotaxis in human leukemic cell lines and human CD34+ progenitors. LPC increased chemotaxis, in cells with high expression of endogenous and exogenous ATX, by at least 80% demonstrating the autocrine effect of ATX expression. Inhibition of ATX using a small molecule inhibitor induced selective killing of ATX-expressing cell lines and reduced the motile phenotype observed in this cells. Our data suggest that the production of bioactive LPA through ATX is involved in controlling proliferation and migration during hematopoiesis and that deregulation contributes to the pathogenesis of AML. AML Classes: Molecular/cytogenetic group of acute myeloid leukemia, either internal tandem duplication (FLT3) or FLT3 point mutation (D835) or normal karyotype (NK) or t(8;21) transclocation (t821) or monosomy 7 (mono7) or inversion on chromosome 16 (inv16) or high leukocyte count normal karyotype (HL). FAB (French-American-British) Classification system for acute myeloid leukemia is provided for each sample.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-1169
refinement:
raw
keywords:
functional genomics
dateModified:
05-03-2014
creators:
Benedikt Brors
availability:
available
types:
gene expression
name:
Homo sapiens
name:
disease state
ID:
A-AFFY-33
name:
Affymetrix GeneChip Human Genome HG-U133A [HG-U133A]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1169/E-MTAB-1169.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1169/E-MTAB-1169.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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