DYNAMICS OF GENE EXPRESSION CHANGES IN THE DEVELOPMENT OF MYELODYSPLASTIC SYNDROMES AND EVOLUTION TO ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Hernandez Sanchez M. 06/09/16; 132743; E1194
Maria Hernandez Sanchez
Contributions
Contributions
Abstract
Abstract: E1194
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders at high risk of developing acute myeloid leukemia (AML). Both disorders are characterized by the accumulation of a wide variety of genetic and epigenetic aberrations in hematopoietic progenitor cells, resulting in altered cell growth and differentiation. However, the molecular mechanisms underlying the evolution of MDS to more aggressive stages remain to be discerned.
Aims
To analyze common deregulated genes and gene pathways, which may potentially be associated with the progression of the disease.
Methods
A multi-platform genome-wide expression profiling was carried out in a series of 73 patients with normal cytogenetics and 17 controls with non-malignant disorders. Two platforms for gene expression analysis were used: the Human Exon 1.0 ST (test group) and the Human Genome U133 Plus 2.0 (validation group) (Affymetrix). The study was based on the analysis of gene expression changes occurring from non-malignant bone marrow conditions through different stages of MDS and towards AML. Two-steps analysis was carried out: (1) Identifying genes which expression levels evolved following an increasing/decreasing trend during the progression of the disease (Normal, Low-Risk MDS, High-Risk MDS and AML); (2) Identifying common expression patterns among the groups of genes with increasing/decreasing trends. At the end, only the genes that appeared deregulated in common with the two platforms were considered.
Results
This methodological approach allowed us to identify common genes and gene pathways that were progressively up-/down-regulated in the transition from non-malignant bone marrow conditions to early MDS stages (Low-Risk MDS), which also remained progressively deregulated during the progression towards advanced MDS (High-Risk MDS) and AML. These genes were classified in 4 major patterns: Pattern 1, MDS/AML-up, included a set of 83 genes that began to be up-regulated in Low-Risk MDS and remained progressively altered during the progression towards High-Risk MDS, with the maximum in AML (NPM1, MYST1, RPL22, RPS6); Pattern 3, AML-up, consisted of 26 progressively up-regulated genes showing the biggest change in their expression level in the transition from High-Risk MDS to AML (HOXA9, MEIS1, FLT3). By contrast, patterns 2 (70 genes) and 4 (32 genes), MDS/AML-down and AML-down, respectively, included those genes that were progressively down-regulated during the evolution of the disease, showing the minimum levels in AML (CEACAM3, CRISP3, CAMP, MMP9). These common and dynamically deregulated genes implicated in the progression of the disease were related to key cellular functions of known relevance in MDS. Thus, apoptosis, DNA damage response, ribosome and translation pathways, and chromatin assembly were progressively up-regulated as the disease progressed, since early MDS stages, while the immune response showed an increasing down-regulation. In addition, the transition from advanced MDS to AML would be characterized by a marked up-regulation of cell proliferation and a differentiation arrest.
Conclusion
The present study demonstrated the presence of a progressive deregulation of several cellular functions, with common deregulated genes, in the transition from non-malignant bone marrow conditions through early and advanced MDS to AML. This evolution seems to occur in an orchestrated way, involving common deregulated functional pathways.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Gene expression profile, Myelodysplasia, Progression
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders at high risk of developing acute myeloid leukemia (AML). Both disorders are characterized by the accumulation of a wide variety of genetic and epigenetic aberrations in hematopoietic progenitor cells, resulting in altered cell growth and differentiation. However, the molecular mechanisms underlying the evolution of MDS to more aggressive stages remain to be discerned.
Aims
To analyze common deregulated genes and gene pathways, which may potentially be associated with the progression of the disease.
Methods
A multi-platform genome-wide expression profiling was carried out in a series of 73 patients with normal cytogenetics and 17 controls with non-malignant disorders. Two platforms for gene expression analysis were used: the Human Exon 1.0 ST (test group) and the Human Genome U133 Plus 2.0 (validation group) (Affymetrix). The study was based on the analysis of gene expression changes occurring from non-malignant bone marrow conditions through different stages of MDS and towards AML. Two-steps analysis was carried out: (1) Identifying genes which expression levels evolved following an increasing/decreasing trend during the progression of the disease (Normal, Low-Risk MDS, High-Risk MDS and AML); (2) Identifying common expression patterns among the groups of genes with increasing/decreasing trends. At the end, only the genes that appeared deregulated in common with the two platforms were considered.
Results
This methodological approach allowed us to identify common genes and gene pathways that were progressively up-/down-regulated in the transition from non-malignant bone marrow conditions to early MDS stages (Low-Risk MDS), which also remained progressively deregulated during the progression towards advanced MDS (High-Risk MDS) and AML. These genes were classified in 4 major patterns: Pattern 1, MDS/AML-up, included a set of 83 genes that began to be up-regulated in Low-Risk MDS and remained progressively altered during the progression towards High-Risk MDS, with the maximum in AML (NPM1, MYST1, RPL22, RPS6); Pattern 3, AML-up, consisted of 26 progressively up-regulated genes showing the biggest change in their expression level in the transition from High-Risk MDS to AML (HOXA9, MEIS1, FLT3). By contrast, patterns 2 (70 genes) and 4 (32 genes), MDS/AML-down and AML-down, respectively, included those genes that were progressively down-regulated during the evolution of the disease, showing the minimum levels in AML (CEACAM3, CRISP3, CAMP, MMP9). These common and dynamically deregulated genes implicated in the progression of the disease were related to key cellular functions of known relevance in MDS. Thus, apoptosis, DNA damage response, ribosome and translation pathways, and chromatin assembly were progressively up-regulated as the disease progressed, since early MDS stages, while the immune response showed an increasing down-regulation. In addition, the transition from advanced MDS to AML would be characterized by a marked up-regulation of cell proliferation and a differentiation arrest.
Conclusion
The present study demonstrated the presence of a progressive deregulation of several cellular functions, with common deregulated genes, in the transition from non-malignant bone marrow conditions through early and advanced MDS to AML. This evolution seems to occur in an orchestrated way, involving common deregulated functional pathways.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Gene expression profile, Myelodysplasia, Progression
Abstract: E1194
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders at high risk of developing acute myeloid leukemia (AML). Both disorders are characterized by the accumulation of a wide variety of genetic and epigenetic aberrations in hematopoietic progenitor cells, resulting in altered cell growth and differentiation. However, the molecular mechanisms underlying the evolution of MDS to more aggressive stages remain to be discerned.
Aims
To analyze common deregulated genes and gene pathways, which may potentially be associated with the progression of the disease.
Methods
A multi-platform genome-wide expression profiling was carried out in a series of 73 patients with normal cytogenetics and 17 controls with non-malignant disorders. Two platforms for gene expression analysis were used: the Human Exon 1.0 ST (test group) and the Human Genome U133 Plus 2.0 (validation group) (Affymetrix). The study was based on the analysis of gene expression changes occurring from non-malignant bone marrow conditions through different stages of MDS and towards AML. Two-steps analysis was carried out: (1) Identifying genes which expression levels evolved following an increasing/decreasing trend during the progression of the disease (Normal, Low-Risk MDS, High-Risk MDS and AML); (2) Identifying common expression patterns among the groups of genes with increasing/decreasing trends. At the end, only the genes that appeared deregulated in common with the two platforms were considered.
Results
This methodological approach allowed us to identify common genes and gene pathways that were progressively up-/down-regulated in the transition from non-malignant bone marrow conditions to early MDS stages (Low-Risk MDS), which also remained progressively deregulated during the progression towards advanced MDS (High-Risk MDS) and AML. These genes were classified in 4 major patterns: Pattern 1, MDS/AML-up, included a set of 83 genes that began to be up-regulated in Low-Risk MDS and remained progressively altered during the progression towards High-Risk MDS, with the maximum in AML (NPM1, MYST1, RPL22, RPS6); Pattern 3, AML-up, consisted of 26 progressively up-regulated genes showing the biggest change in their expression level in the transition from High-Risk MDS to AML (HOXA9, MEIS1, FLT3). By contrast, patterns 2 (70 genes) and 4 (32 genes), MDS/AML-down and AML-down, respectively, included those genes that were progressively down-regulated during the evolution of the disease, showing the minimum levels in AML (CEACAM3, CRISP3, CAMP, MMP9). These common and dynamically deregulated genes implicated in the progression of the disease were related to key cellular functions of known relevance in MDS. Thus, apoptosis, DNA damage response, ribosome and translation pathways, and chromatin assembly were progressively up-regulated as the disease progressed, since early MDS stages, while the immune response showed an increasing down-regulation. In addition, the transition from advanced MDS to AML would be characterized by a marked up-regulation of cell proliferation and a differentiation arrest.
Conclusion
The present study demonstrated the presence of a progressive deregulation of several cellular functions, with common deregulated genes, in the transition from non-malignant bone marrow conditions through early and advanced MDS to AML. This evolution seems to occur in an orchestrated way, involving common deregulated functional pathways.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Gene expression profile, Myelodysplasia, Progression
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders at high risk of developing acute myeloid leukemia (AML). Both disorders are characterized by the accumulation of a wide variety of genetic and epigenetic aberrations in hematopoietic progenitor cells, resulting in altered cell growth and differentiation. However, the molecular mechanisms underlying the evolution of MDS to more aggressive stages remain to be discerned.
Aims
To analyze common deregulated genes and gene pathways, which may potentially be associated with the progression of the disease.
Methods
A multi-platform genome-wide expression profiling was carried out in a series of 73 patients with normal cytogenetics and 17 controls with non-malignant disorders. Two platforms for gene expression analysis were used: the Human Exon 1.0 ST (test group) and the Human Genome U133 Plus 2.0 (validation group) (Affymetrix). The study was based on the analysis of gene expression changes occurring from non-malignant bone marrow conditions through different stages of MDS and towards AML. Two-steps analysis was carried out: (1) Identifying genes which expression levels evolved following an increasing/decreasing trend during the progression of the disease (Normal, Low-Risk MDS, High-Risk MDS and AML); (2) Identifying common expression patterns among the groups of genes with increasing/decreasing trends. At the end, only the genes that appeared deregulated in common with the two platforms were considered.
Results
This methodological approach allowed us to identify common genes and gene pathways that were progressively up-/down-regulated in the transition from non-malignant bone marrow conditions to early MDS stages (Low-Risk MDS), which also remained progressively deregulated during the progression towards advanced MDS (High-Risk MDS) and AML. These genes were classified in 4 major patterns: Pattern 1, MDS/AML-up, included a set of 83 genes that began to be up-regulated in Low-Risk MDS and remained progressively altered during the progression towards High-Risk MDS, with the maximum in AML (NPM1, MYST1, RPL22, RPS6); Pattern 3, AML-up, consisted of 26 progressively up-regulated genes showing the biggest change in their expression level in the transition from High-Risk MDS to AML (HOXA9, MEIS1, FLT3). By contrast, patterns 2 (70 genes) and 4 (32 genes), MDS/AML-down and AML-down, respectively, included those genes that were progressively down-regulated during the evolution of the disease, showing the minimum levels in AML (CEACAM3, CRISP3, CAMP, MMP9). These common and dynamically deregulated genes implicated in the progression of the disease were related to key cellular functions of known relevance in MDS. Thus, apoptosis, DNA damage response, ribosome and translation pathways, and chromatin assembly were progressively up-regulated as the disease progressed, since early MDS stages, while the immune response showed an increasing down-regulation. In addition, the transition from advanced MDS to AML would be characterized by a marked up-regulation of cell proliferation and a differentiation arrest.
Conclusion
The present study demonstrated the presence of a progressive deregulation of several cellular functions, with common deregulated genes, in the transition from non-malignant bone marrow conditions through early and advanced MDS to AML. This evolution seems to occur in an orchestrated way, involving common deregulated functional pathways.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Gene expression profile, Myelodysplasia, Progression
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