Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280988 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:STAT3β is a tumor suppressor in acute myeloid leukemia
| PRJNA484895 | ENA
Project description:<p>Patients with myeloid malignancies bearing high-risk cytogenetic abnormalities lack effective therapies and have a poor overall survival. -7/del(7q) is identified in half of high-risk myeloid neoplasms. We recently identified <i>CUX1</i> to be a haploinsufficient myeloid tumor suppressor gene located within the commonly deleted segment of 7q22. Here we identify the spectrum of somatic mutations that co-occur with loss of <i>CUX1</i> and chromosome 7 in patients with <i>de novo</i> acute myeloid leukemia (AML) or a therapy-related myeloid neoplasm. -7/del(7q) leukemias have a distinct mutational profile characterized by low frequencies of alterations in major leukemogenic pathways, including genes encoding transcription factors, cohesin, and DNA-methylation-related proteins. In contrast, RAS pathway activating mutations occurred in 40% of -7/del(7q) samples, a significantly higher frequency than other AMLs and higher than previously reported. As targeted therapeutics advance, our data provide guidance for which pathways are most relevant in the treatment of adverse-risk myeloid leukemia. </p>
| phs000759 | dbGaP
Project description:DNA methylation profiling in acute myeloid leukemia
| PRJNA324564 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE31941: Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [gene expression] GSE32251: Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [methylation] Refer to individual Series
2011-09-20 | E-GEOD-32252 | biostudies-arrayexpress
Project description:Loss of chromosome 7 and del(7q) [-7/del(7q)] are recurring cytogenetic abnormalities in hematologic malignancies, including acute myeloid leukemia and therapy-related myeloid neoplasms, and associated with an adverse prognosis. We performed SNP array analysis on de novo and therapy-related myeloid neoplasms and identified a 2.17 Mb commonly deleted segment on chromosome band 7q22.1 containing CUX1, a gene encoding a homeodomain-containing transcription factor. Haploinsufficiency of the highly conserved ortholog, cut, led to hemocyte overgrowth and tumor formation in Drosophila melanogaster. Similarly, haploinsufficiency of CUX1 gave human hematopoietic cells a significant engraftment advantage upon transplantation into immunodeficient mice. These data identify CUX1 as a conserved, haploinsufficient tumor suppressor frequently deleted in myeloid neoplasms. We performed SNP-array analysis of 34 primary patient samples with de novo or therapy-related myeloid leukemia and one acute myeloid leukemia cell line, UoCM1. For patient samples, DNA was obtained from the white blood cells of bone marrow or peripheral blood leukemia specimens. Cytogenetic analysis revealed clonal -7/del(7q) in 17 of the cases.
2012-11-24 | E-GEOD-42482 | biostudies-arrayexpress
Project description:DNA methylation analysis of acute myeloid leukemia (AML)
| PRJNA670857 | ENA
Project description:DNA methylation is tightly regulated throughout mammalian development and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO induced AML. Using this model, we show that the primary effect of Tet2 loss in pre-leukemic hematopoietic cells is progressive and widespread DNA hypermethylation affecting up to 25% of active enhancer elements. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner, but increase relative to population doublings. We confirm this specific enhancer hypermethylation phenotype in human AML patients with TET2 mutations. Analysis of immediate gene expression changes reveals rapid deregulation of a large number of genes implicated in tumorigenesis, including many downregulated tumor suppressor genes. Hence, we propose that TET2 prevents leukemic transformation by protecting enhancers from aberrant DNA methylation, and that it is the combined silencing of several tumor suppressor genes in TET2-mutated hematopoietic cells that contribute to increased stem cell proliferation and leukemogenesis. Gene expression profiles (Agilent SurePrint G3 Mouse GE 8x60K arrays) of FACS-sorted in vivo GMP cells (Lin-cKit+Sca1-CD16/32+CD150-) isolated from bone marrow of recipient mice one month after transplantation of WT bone marrow or splenic cells from two independent moribond Tet2-/-:AE leukemic mice (LeuA/AE1), or LeuB/AE3)
2015-04-30 | E-GEOD-68415 | biostudies-arrayexpress
Project description:Regulation of p21 by TWIST2 contributes to its tumor suppressor function in human acute myeloid leukemia
| PRJNA246310 | ENA
Project description:Genome-wide DNA methylation profiling of Acute Myeloid Leukemia
| PRJNA121487 | ENA