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Expression data from murine hematopoietic cells expressing BCR-ABL alone, NUP98-HOXA9 alone, BCR-ABL and NUP98-HOXA9, or null for both oncogenes

ABSTRACT: Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown. Using a genetically defined mouse model of acute leuekmia, we investigated the regulated of genes downstream of the cooperative oncogenic interaction between BCR-ABL and NUP98-HOXA9 and identified a unique gene signature abberrantly expression in leukemia.

ORGANISM(S): Mus musculus

PROVIDER: GSE37907 | GEO | 2012/05/11

SECONDARY ACCESSION(S): PRJNA165663

REPOSITORIES: GEO

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Expression data from murine hematopoietic cells expressing BCR-ABL alone, NUP98-HOXA9 alone, BCR-ABL and NUP98-HOXA9, or null for both oncogenes

Project description:Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown. Using a genetically defined mouse model of acute leuekmia, we investigated the regulated of genes downstream of the cooperative oncogenic interaction between BCR-ABL and NUP98-HOXA9 and identified a unique gene signature abberrantly expression in leukemia. Total RNA was isolated from hematopoietic cells transduced with BCR-ABL and Nup98-HOXA9 retroviruses and transplanted into recipient mice. Bone marrow cells were purified by GFP (BCR-ABL) and YFP (NUP98-HOXA9) using FACS.

2012-05-10 | E-GEOD-37907 | biostudies-arrayexpress

MLL is essential for NUP98-HOXA9-induced leukemia

Project description:Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.

2017-02-28 | GSE93923 | GEO

NUP98-HOXA9 acute myeloid leukemia

Project description:Mass Spectrometry analysis of the interactome of the oncoprotein NUP98-HOXA9

2017-07-10 | PXD001828 | Pride

Effect of NOX2 (CYBB) knock out on the transcriptome of leukemia stem cells isolated from NUP98/HOXA9+BCR/ABL murine syngeneic leukemia model

Project description:To investigate the function of NOX2 (CYBB) in leukemia stem cells, we created leukemia by tranforming primitive hematopoetic cells isolated from wild type and NOX2-KO mice with NUP98/HOXA9 and BCR/ABL oncogenes, isolated mRNA, and performed RNA-seq experiments to profile transcriptional changes upon NOX2 loss.

2019-03-26 | GSE117657 | GEO

Evaluation of the NUP98-HOXA9 role as oncogenic transcription factor

Project description:To study the oncogenic mechanism triggered by the leukemic fusion protein NUP98-HOXA9, we cloned the cDNA of NUP98-HOXA9 into a retroviral vector (pMSCV-IRES-GFP) and efficiently transduced the HEK293FT human cell line. We performed a ChIP-seq analysis to identify the DNA binding sites of NUP98-HOXA9. These results allowed us to demonstrate that NUP98-HOXA9 regulates the expression of genes involved in the development of Acute Myeloid Leukemia by directly interacting with their enhancer regions. We further investigated the functional contribution to the DNA binding profile of the two moieties that compose the fusion protein. We cloned the coding region of HOXA9 wt and NUP98 wt in the same retroviral vector, established two new cellular models, 293FT-HOXA9 and 293FT-NUP98, and performed separate ChIP-seq analyses. We demonstrated that both moieties contribute importantly to the regulation of the target genes.

2016-12-31 | GSE62586 | GEO

Development of NUP98-HOXA9 gene expression signatures

Project description:To explore the molecular mechanisms induced by the leukemic fusion protein NUP98-HOXA9, we performed gene expression analysis of human hematopoietic progenitors and primary samples of patients that express NUP98-HOXA9. By combining these data with ChIP-seq results, we observed that the fusion protein is able to both activate and repress the expression of its target genes.

2016-12-31 | GSE62585 | GEO

Gene expression profiling of NUP98-HOXA9 expressing mouse embryonic stem cells

Project description:To investigate the effect of NUP98-HOXA9 on global gene expression, we established FLAG-NUP98-HOXA9 expressing mouse embryonic stem cell lines.

2023-07-25 | GSE227199 | GEO

Transcription profiling of mouse bone marrow cells expressing NUP98/HHEX or NUP98/HOXA9 a new oncogenic fusion with acute myeloid leukemia

Project description:We have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells. Experiment Overall Design: Murine bone marrow cells were transduced with a retrovirus (MSCV-IRES-GFP, MIG) expressing either NUP98/HHEX or NUP98/HOXA9 (or the empty vector), mRNA was isolated after 72h. Each experiment was performed in triplicates.

2008-06-11 | E-GEOD-10909 | biostudies-arrayexpress

Gene expression changes upon Mll1 knockout in NUP98-HOXA9 transformed murine LSKs

Project description:We report Illumina next generation RNA sequencing (RNAseq) of NUP98-HOXA9 in vitro transformed murine LSKs upon genetic deletion of Mll1. These gene expression data illustrate that Mll1 regulates Hoxa, Hoxb and Meis1 expression in NUP98-HOXA9 transformed murine BM cells.

2016-12-11 | GSE75997 | GEO

Phase Separation by the NUP98-HOXA9 Fusion Oncoprotein Drives an Oncogenic Phenotype in Hematopoietic Cells

Project description:RNA-seq of mouse hematopoietic stem and progenitor cells expressing NUP98-HOXA9 (NHX9) show upregulation of HOX and other NUP98 fusion target genes, but expression changes are dampened or lost with the introduction of mutations in NUP98's FG repeats or HOXA9's DNA binding domain

2021-10-13 | GSE185621 | GEO

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