Transcriptomics,Genomics

Dataset Information

23

MLL is essential for NUP98-HOXA9-induced leukemia


ABSTRACT: 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. Overall design: To identify the regulated genes by the NUP98 moiety of NUP98-HOXA9, we performed gene expression profiling in full-length NUP98-HOXA9- and NUP98-HOXA9 deletion mutant-expressing cells.

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

SUBMITTER: Yutaka Shima  

PROVIDER: GSE93923 | GEO | 2017-02-28

SECONDARY ACCESSION(S): PRJNA362844

REPOSITORIES: GEO

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Publications

MLL is essential for NUP98-HOXA9-induced leukemia.

Shima Y Y   Yumoto M M   Katsumoto T T   Kitabayashi I I  

Leukemia 20170217 10


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 mixed lineage leukemia (MLL) via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immorta  ...[more]

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