Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA114579 | ENA |
REPOSITORIES: ENA
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Project description:Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells; The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Refer to individual Series Experiment Overall Design: This SuperSeries is composed of the following subset Series: Experiment Overall Design: GSE13690: Gene expression profiling of murine MLL leukemias (whole BM) Experiment Overall Design: GSE13692: Expression profiling of MLL-AF10 myeloid leukemia cellular subsets Experiment Overall Design: GSE13693: Gene expression profiling of normal mouse myeloid cell populations
2009-02-21 | E-GEOD-13796 | biostudies-arrayexpress
Project description:Cooperation of MLL/AF10 with RAS pathway mutations accelerated myeloid leukemia development. The detail molecular mechanism is analyzed by identification of the differentially expressed genes between MLL/AF10 cells harboring wild-type and mutant RAS pathway genes and by with or without Hoxa11. We used cDNA microarray to compare transcriptomes between mouse MLL/AF10 myeloid leukemia cells harboring wild-type KRAS and harboring KRAS-G12C (AKw1G and AK3G), or between MLL/AF10 cells harboring wild-type PTPN11 and harboring PTPN11-G503A (APw-1 and APm-1), or between MLL/AF10 cells without and with Hoxa11 (12G-V and 12G-H11).
2020-07-01 | GSE134586 | GEO
Project description:The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Samples are from five separate cohorts of mice where leukemia was initiated using distinct MLL fusion oncogenes: MLL-AF1p (n=9), MLL-AF10 (n=8), MLL-GAS7 (n=5), MLL-AF9 (n=5) and MLL-ENL (n=7). Four normal BM samples were also used as controls.
2009-02-21 | E-GEOD-13690 | biostudies-arrayexpress
Project description:Assesment of gene expression upon AF10 deletion in MLL-AF9 secondary leukemia
| PRJNA236784 | ENA
Project description:Chromaitn immunoprecipitation of myeloid progenitors immortalized by HOXA9 or MLL-AF10
| PRJDB9726 | ENA
Project description:Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes. Primary MLL-AF9 leukemias in the AF10 floxed background (homozygous) were transduced with MSCV-IRES-tdTomato (MIT) or the Cre recombinase expressing MIT vector, cells were sorted and injected into secondary recipient mice to generate Af10 floxed (MIT) or deleted (CRE) leukemias. BM cells fresly harvested from these leukemias were sorted for tdTomato expression and used for microarrays. BM cells from Hoxa9-Meis1 transduced primary leukemias were used for comparison.
2014-09-08 | E-GEOD-54499 | biostudies-arrayexpress
Project description:Expression Profiling of a CALM/AF10 leukemia mouse model
| PRJNA95819 | ENA
Project description:Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes.
2014-09-08 | GSE54499 | GEO
Project description:Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils. Experiment Overall Design: Leukemic splenocytes from four mice with MLL-AF10 AML were sub-fractionated in to c-kit high and c-kit negative sub-populations by FACS.
2009-02-21 | E-GEOD-13692 | biostudies-arrayexpress
Project description:The translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.
2017-06-19 | GSE58853 | GEO