Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression

Bar, Merav and Stirewalt, Derek L. and Pogosova-Agadjanyan, Era L. and Wagner, Vitas and Gooley, Ted A and Abbasi, Nissa and Bhatia, Ravi and Deeg, H. Joachim and Radich, Jerald P. (2008) Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression. Translational Oncogenomics, 3. pp. 137-149. ISSN 1177-2727

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Abstract

The myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. The genetic and epigenetic pathways that determine disease stage and progression are largely unknown. In the current study we used gene expression microarray methodology to examine the gene expression differences between normal hematopoietic cells and hematopoietic cells from patients with MDS at different disease stages, using both unselected and CD34+ selected cells. Signifi cant differences between normal and MDS ematopoietic cells were observed for several genes and pathways. Several genes promoting or opposing apoptosis were dysregulated in MDS cases, most notably MCL1 and EPOR. Progression from RA to RAEB(T) was associated with increased expression of several histone genes. In addition, the RAR-RXR pathway, critical for maintaining a balance between self-renewal and differentiation of hematopoietic stem cells, was found to be deregulated in hematopoietic cells from patients with advanced MDS compared to patients with refractory anemia. These fi ndings provide new insights into the understanding of the pathophysiology and progression of MDS, and may guide to new targets for therapy. Taken together with previous published data, the present results also underscore the considerable complexity of the regulation of gene expression in MDS.

Item Type:	Article or Abstract
Additional Information:	This journal is not yet indexed by PubMed - Medline.
PubMed ID:	20396593
NIHMSID:	NIHMS89695
PMCID:	PMC2854514
Grant Numbers:	P01 CA018029-260026, P01 CA018029-310026 , P01 CA018029-320047, P01 CA018029-33 , R01 HL082941-04, P01 HL036444-280016, P01 HL036444-250013 , P01 HL036444-27
Depositing User:	Library Staff
Date Deposited:	29 Jan 2009 19:35
Last Modified:	14 Feb 2012 14:42
URI:	http://authors.fhcrc.org/id/eprint/245

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