Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA188264 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Screening Protocol and Longitudinal Study Of Bone Marrow Failure Syndromes And Cytopenias - BMFC 5401
| PRJNA188263 | ENA
Project description:Inherited Bone Marrow Failure Syndromes
| PRJNA417130 | ENA
Project description:Inherited Bone Marrow Failure Syndromes
| PRJNA417131 | ENA
Project description:Genomic changes in Bone marrow failure Syndromes.
| PRJNA808814 | ENA
Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized variably by the presence of peripheral cytopenias, bone marrow hypercellularity and dysplastic changes in the bone marrow. While MDS patients have an increased risk of progression to acute myeloid leukemia (AML), most MDS patients actually succumb to progressive bone marrow failure. Amongst patients classified as low-risk MDS, different clinical evolutions have been observed, with some patients remaining relatively stable for long periods of time (herein, stable MDS), while others show more progressive disease, with worsening cytopenias, and often increased transfusion requirements (herein, progressive MDS). Current risk stratification strategies fail to distinguish these two groups at diagnosis. We report here that these distinct behaviors are encoded at the epigenetic level and that examining DNA methylation profiles of low-risk MDS patients captures underlying differences between the two different groups. In this study, we identified 356 differentially methylated regions (DMRs) between stable and progressive low-risk MDS at the time of diagnosis. The number of DMRs was almost doubled at the time of progression (681 follow-up DMRs), and this was accompanied by an increase in the local variability at specific methylation regions, and an increase in heterogeneity over time. These findings reveal previously unrecognized epigenetic heterogeneity in low-risk MDS patients and opens the possibility for using epigenetic differences to help improve risk-stratification at diagnosis.
2020-04-14 | GSE108247 | GEO
Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 55 samples from 54 patients that were genotyped with Omni1-Quad. Illumina Infinium SNP-A genotyping was performed on DNA extracted from bone marrow aspirates using standard manufacturer's protocol
2014-01-01 | E-GEOD-48482 | biostudies-arrayexpress
Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 67 samples from 51 patients that were genotyped with Illumina Quad610 Beadchip. Illumina Infinium SNP-A genotyping was performed on DNA extracted from bone marrow aspirates using standard manufacturer's protocol
2014-01-01 | E-GEOD-48483 | biostudies-arrayexpress
Project description:Dyskeratosis congenita (DKC) and idiopathic aplastic anemia (AA) are bone marrow failure syndromes that share characteristics of premature aging with severe telomere attrition. In this study, we analyzed blood samples of 62 AA and 13 DKC patients to demonstrate that their epigenetic age predictions are overall increased, albeit not directly correlated with telomere length. Aberrant DNA methylation was observed in the gene PRDM8 in DKC and AA as well as in other diseases with premature aging phenotype, such as Down syndrome, Werner syndrome and Hutchinson-Gilford-Progeria syndrome. To gain further insight into the functional relevance of PRDM8 we generated induced pluripotent stem cells (iPSCs) with heterozygous and homozygous knockout. Loss of PRDM8 impaired hematopoietic and neuronal differentiation of iPSCs, but it did not impact on epigenetic age. Taken together, aberrant DNA methylation in PRDM8 provides a biomarker for bone marrow failure syndromes, which may contribute to the hematopoietic and neuronal phenotypes of premature aging syndromes.
2020-08-31 | GSE141107 | GEO
Project description:Dyskeratosis congenita (DKC) and idiopathic aplastic anemia (AA) are bone marrow failure syndromes that share characteristics of premature aging with severe telomere attrition. In this study, we analyzed blood samples of 62 AA and 13 DKC patients to demonstrate that their epigenetic age predictions are overall increased, albeit not directly correlated with telomere length. Aberrant DNA methylation was observed in the gene PRDM8 in DKC and AA as well as in other diseases with premature aging phenotype, such as Down syndrome, Werner syndrome and Hutchinson-Gilford-Progeria syndrome. To gain further insight into the functional relevance of PRDM8 we generated induced pluripotent stem cells (iPSCs) with heterozygous and homozygous knockout. Loss of PRDM8 impaired hematopoietic and neuronal differentiation of iPSCs, but it did not impact on epigenetic age. Taken together, aberrant DNA methylation in PRDM8 provides a biomarker for bone marrow failure syndromes, which may contribute to the hematopoietic and neuronal phenotypes of premature aging syndromes.
2020-08-31 | GSE141106 | GEO
Project description:Myelodysplastic syndromes (MDS) are a group of hematologic neoplasms in which the bone marrow fails to produce enough mature blood cells, leading to peripheral blood cytopenias and myeloproliferation1-3. The average survival time following diagnosis of MDS is 2.5 years4, owing to few treatment options5. Roughly 20-30% of MDS patients progress to acute myeloid leukemia6. Risks of allogeneic bone marrow transplants in elderly patients, together with a dearth of effective FDA-approved drugs, make it imperative to revisit the origins of hematopoietic differentiation defects underlying MDS to identify new druggable targets7-9. We recently reported that haploinsufficiency of the atypical kinase Riok2 (Right open reading frame kinase 2)10 in mice leads to anemia and MDS-associated phenotypes11. However, the underlying molecular mechanisms remain largely unexplored. Here we show that RIOK2 is a master transcription factor that not only drives erythroid lineage commitment, but simultaneously suppresses megakaryocytic and myeloid lineages in primary human stem and progenitor cells. Structural modeling, chromatin immunoprecipitation sequencing, ATAC-sequencing and structure-function domain deletion mutants revealed that RIOK2 activates or represses specific genetic programs in hematopoiesis via its previously unappreciated winged helix-turn-helix DNA-binding domain and two transactivation domains. Mechanistically, RIOK2 functions as a master regulator of hematopoietic lineage commitment by controlling the expression of key lineage-specific transcription factors, such as GATA1, GATA2, SPI1, RUNX3 and KLF1. We also show that GATA1 and RIOK2 function in a positive feedback loop to drive erythroid differentiation. These discoveries present novel therapeutic opportunities to correct hematopoietic differentiation defects in MDS, in the anemia of chronic diseases such as renal failure and inflammation, and in other bone marrow failure disorders.
2021-10-16 | MSV000088238 | MassIVE