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Series GSE38687 Query DataSets for GSE38687
Status Public on Jul 22, 2012
Title Idh1-R132H mutation increases murine hematopoietic progenitors and alters epigenetics.
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequent in human glioblastomas1 and cytogenetically normal acute myeloid leukemias (AML)2. These alterations are gain-of-function mutations in that they drive the synthesis of the “oncometabolite” R-2-hydroxyglutarate (2HG)3. It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukemogenesis. Here we report the characterization of conditional knock-in mice in which the most common IDH1 mutation, Idh1-R132H, is inserted into the endogenous murine Idh1 locus and is expressed in cells of the hematopoietic (Vav-KI) or more specifically in cells of the myeloid (LysM-KI) lineage. These mutants show increased numbers of early hematopoietic progenitors and develop splenomegaly and anemia with extramedullary hematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells exhibit both hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1/2-mutant AML. Thus, our study is the first to describe the generation of conditional Idh1-R132H-KI mice. Furthermore, our study is also the first report showing the induction of a leukemic DNA methylation signature in a modeled system and sheds light on the mechanistic links between IDH1 mutation and human AML.
Overall design DNA methylation profiling in LSK cells from IDH1-R132H knock-in mice vs. control mice
Contributor(s) Sasaki M, Knobbe CB, Mak T, Figueroa ME, Melnick A
Citation(s) 22763442
Submission date Jun 13, 2012
Last update date May 15, 2019
Contact name Maria Eugenia Figueroa
Organization name University of Miiami
Department Human Genetics
Lab Maria Figueroa
Street address 1501 NW 10th Ave, BRB 709A, Locator code C227
City Miami
State/province FL
ZIP/Postal code 33136
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (5)
GSM947547 UR12_Idh1-R132H
GSM947548 UR9_Idh1-R132H
GSM947549 UR16_Idh1-R132H
BioProject PRJNA168439
SRA SRP013732

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Supplementary file Size Download File type/resource
GSE38687_RAW.tar 46.7 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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