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Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse model of AML - hierarchical maintenance of MLL myeloid leukemia stem cells

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Tim Somervaille

PROVIDER: E-GEOD-13796 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of mouse MLL leukemias (whole BM)

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.

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