Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression profiling of murine hemopoietic cell survival on cDNA arrays.

ABSTRACT: Deregulated cell survival programs are a classical hallmark of cancer. We have previously identified a serine residue (Ser585) in the beta-c subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor that selectively and independently promotes cell survival. We now show that Ser585 phosphorylation is constitutive in 20/23 (87%) acute myeloid leukemia (AML) patient samples indicating that this survival-only pathway is frequently deregulated in leukemia. We performed a global expression screen to identify gene targets of this survival pathway and report a 138-gene beta-c Ser585-regulated transcriptome. Pathway analysis defines a gene network enriched for PI 3-kinase target genes as well as a cluster of genes involved in cancer and cell survival. factorial design; factors: time x 2 & mutation, same RNA was used in both GSE18220 & GSE18221

ORGANISM(S): Mus musculus

SUBMITTER: Kirsten Herbert

PROVIDER: E-GEOD-18221 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML.

Powell Jason A JA Thomas Daniel D Barry Emma F EF Kok Chung H CH McClure Barbara J BJ Tsykin Anna A To L Bik LB Brown Anna A Lewis Ian D ID Herbert Kirsten K Goodall Gregory J GJ Speed Terence P TP Asou Norio N Jacob Bindya B Osato Motomi M Haylock David N DN Nilsson Susan K SK D'Andrea Richard J RJ Lopez Angel F AF Guthridge Mark A MA

Blood 20091005 23

Deregulated cell survival programs are a classic hallmark of cancer. We have previously identified a serine residue (Ser585) in the betac subunit of the granulocyte-macrophage colony-stimulating factor receptor that selectively and independently promotes cell survival. We now show that Ser585 phosphorylation is constitutive in 20 (87%) of 23 acute myeloid leukemia (AML) patient samples, indicating that this survival-only pathway is frequently deregulated in leukemia. We performed a global expres ...[more]

PMID: 19805619

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Project description:Background: MicroRNAs are regulators of gene expression, mainly functioning by decreasing mRNA levels of their multiple targets. Deregulated microRNA expression has been shown for acute myeloid leukemia, a disease also characterized by altered gene expression associated with distinct genomic aberrations such as nucleophosmin (NPM1) mutations. To further illuminate the role of deregulated microRNA and gene expression in cytogenetically normal acute myeloid leukemia with NPM1 mutation, we performed an integrative analysis of microRNA and mRNA expression data sets. Design and Methods: Both microRNA and gene expression profiles were measured in a cohort of 43 adult acute myeloid leukemia patient samples (n=42 cytogenetically normal, n=1 del7q; median age 46 years [range 23-60]) of known NPM1 mutation status (n=23 mutated, n=20 wild-type) and data integratively analyzed. Putative microRNA-mRNA interactions were validated by quantitative RT-PCR, Western Blot and luciferase reporter assays. For selected microRNAs, sensitivity of microRNA-overexpressing cells to cytarabine treatment was tested by FACS viability and cell proliferation assays. Results: Our integrative approach of analyzing both microRNA and gene expression profiles in parallel resulted in a refined list of putative target genes affected by NPM1 mutation-associated microRNA deregulation. Of 177 putative microRNA - target mRNA interactions, we could identify and validate 77 novel candidates with known or potential implication in leukemogenesis, such as IRF2-miR-20a, KIT-miR-20a and MN1-miR-15a. Furthermore, our data showed that deregulated expression of tumor suppressor microRNAs such as miR-29a and miR-30c might contribute to the sensitivity to cytarabine, which is observed in NPM1-mutated acute myeloid leukemia. Conclusions: Overall, our observations highlight that integrative data analysis approaches can improve insights into leukemia biology, and lead to the identification of novel microRNA - target gene interactions of potential relevance for acute myeloid leukemia treatment. MicroRNA and gene expression profiles were measured in a cohort of 43 adult (42 cytogenetically normal and 1 del7q) acute myeloid leukemia patient samples of known NPM1 mutation status (n=23 mutated, n=20 wild-type). This submission represents the mRNA expression component of the study. The miRNA expression data will be deposited as supplementary information along with the accompanying manuscript.

Dataset Information

Expression profiling of murine hemopoietic cell survival on cDNA arrays.

Publications

Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML.

Similar Datasets

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