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

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...

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Autores principales: Bar, Merav, Stirewalt, Derek, Pogosova-Agadjanyan, Era, Wagner, Vitas, Gooley, Ted, Abbasi, Nissa, Bhatia, Ravi, Deeg, H. Joachim, Radich, Jerald
Formato: Texto
Lenguaje:English
Publicado: Libertas Academica 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854514/
https://www.ncbi.nlm.nih.gov/pubmed/20396593
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author Bar, Merav
Stirewalt, Derek
Pogosova-Agadjanyan, Era
Wagner, Vitas
Gooley, Ted
Abbasi, Nissa
Bhatia, Ravi
Deeg, H. Joachim
Radich, Jerald
author_facet Bar, Merav
Stirewalt, Derek
Pogosova-Agadjanyan, Era
Wagner, Vitas
Gooley, Ted
Abbasi, Nissa
Bhatia, Ravi
Deeg, H. Joachim
Radich, Jerald
author_sort Bar, Merav
collection PubMed
description 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. Significant differences between normal and MDS hematopoietic 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 findings 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.
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spelling pubmed-28545142010-04-14 Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression Bar, Merav Stirewalt, Derek Pogosova-Agadjanyan, Era Wagner, Vitas Gooley, Ted Abbasi, Nissa Bhatia, Ravi Deeg, H. Joachim Radich, Jerald Transl Oncogenomics Original Research 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. Significant differences between normal and MDS hematopoietic 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 findings 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. Libertas Academica 2008-05-29 /pmc/articles/PMC2854514/ /pubmed/20396593 Text en © 2008 The authors. http://creativecommons.org/licenses/by/3.0 This article is published under the Creative Commons Attribution By licence. For further information go to: http://creativecommons.org/licenses/by/3.0. (http://creativecommons.org/licenses/by/3.0)
spellingShingle Original Research
Bar, Merav
Stirewalt, Derek
Pogosova-Agadjanyan, Era
Wagner, Vitas
Gooley, Ted
Abbasi, Nissa
Bhatia, Ravi
Deeg, H. Joachim
Radich, Jerald
Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title_full Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title_fullStr Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title_full_unstemmed Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title_short Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression
title_sort gene expression patterns in myelodyplasia underline the role of apoptosis and differentiation in disease initiation and progression
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854514/
https://www.ncbi.nlm.nih.gov/pubmed/20396593
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