Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA122713 | ENA |
REPOSITORIES: ENA
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Project description:Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
2016-06-17 | GSE83449 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16676: Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1 GSE16677: Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples GSE16679: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia GSE16682: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors GSE16684: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling Refer to individual Series
2010-08-01 | E-GEOD-16655 | biostudies-arrayexpress
Project description:Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation. DNA methylation profiles obtained at different stages of the development of Down syndrome AMKL and from CD41+ cells from partial trisomic mice
2013-08-19 | E-GEOD-46167 | biostudies-arrayexpress
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.
2010-08-01 | GSE16677 | GEO
Project description:To identify the spectrum of gene mutations in Down syndrome-related myeloid disorders, whole genome sequencing of 4 trio samples from TAM/AMKL/complete remission (CR) phases and whole exome sequencing of 15 TAM and 14 DS-AMKL samples were performed.
| EGAS00001000546 | EGA
Project description:Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation.
2013-08-19 | GSE46167 | GEO
Project description:Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS fetal livers precedes the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes due trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Correlation of gene expression changes caused by Erg trisomy in Ts(1716)65Dn multilineage progenitor cells with those associated with trisomy 21 in human DS HSCs support a role for ERG as a regulator of hematopoietic lineage potential, trisomy of which drives pre-leukemic changes in DS fetal livers that predispose to subsequent DS-TMD and DS-AMKL.
2015-04-15 | E-MTAB-2574 | biostudies-arrayexpress
Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors
2013-03-29 | GSE45619 | GEO
Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors
2013-03-29 | GSE45618 | GEO
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples. The leukemic blasts were sorted based on CD41, CD7, CD117, CD33, and CD34 antibodies as previously described (Klin. Padiatr. 217, 126-134).
2010-08-01 | E-GEOD-16677 | biostudies-arrayexpress