Transcriptomics

Dataset Information

297

MiR-126 Orchestrates an Oncogenic Program in B-Cell Precursor Acute Lymphoblastic Leukemia


ABSTRACT: MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden. Study 1: Turning off miR-126 expression from an experimental murine B-ALL in vivo; Study 2: Modulation of miR-126 expression in human cord blood stem and progenitor cell populations in vitro.

ORGANISM(S): Musculus  

SUBMITTER: Cristiana Fanciullo   Silvia Nucera  Davide Cittaro  Tiziana Plati  Jose Manuel Garcia-Manteiga  Francesco E Boccalatte  Alice Giustacchini  Jose M Garcia-Manteiga  Bernhard Gentner  Luigi Naldini 

PROVIDER: E-GEOD-78078 | ArrayExpress | 2016-06-14

SECONDARY ACCESSION(S): SRP070532GSE78078PRJNA312538

REPOSITORIES: GEO, ArrayExpress, ENA

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MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression  ...[more]

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