NUP98 fusion proteins interact with the NSL and MLL1 complexes to drive leukemogenesis Journal Article


Authors: Xu, H.; Valerio, D. G.; Eisold, M. E.; Sinha, A.; Koche, R. P.; Hu, W.; Chen, C. W.; Chu, S. H.; Brien, G. L.; Park, C. Y.; Hsieh, J. J.; Ernst, P.; Armstrong, S. A.
Article Title: NUP98 fusion proteins interact with the NSL and MLL1 complexes to drive leukemogenesis
Abstract: The nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in multiple hematopoietic malignancies. Here, we demonstrate that NUP98 fusion proteins, including NUP98-HOXA9 (NHA9), NUP98-HOXD13 (NHD13), NUP98-NSD1, NUP98-PHF23, and NUP98-TOP1 physically interact with mixed lineage leukemia 1 (MLL1) and the non-specific lethal (NSL) histone-modifying complexes. Chromatin immunoprecipitation sequencing illustrates that NHA9 and MLL1 co-localize on chromatin and are found associated with Hox gene promoter regions. Furthermore, MLL1 is required for the proliferation of NHA9 cells in vitro and in vivo. Inactivation of MLL1 leads to decreased expression of genes bound by NHA9 and MLL1 and reverses a gene expression signature found in NUP98-rearranged human leukemias. Our data reveal a molecular dependency on MLL1 function in NUP98-fusion-driven leukemogenesis. © 2016 Elsevier Inc.
Keywords: leukemia; hox gene; mixed lineage leukemia 1; non-specific lethal histone-modifying complexes; nup98 fusion
Journal Title: Cancer Cell
Volume: 30
Issue: 6
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2016-12-12
Start Page: 863
End Page: 878
Language: English
DOI: 10.1016/j.ccell.2016.10.019
PROVIDER: scopus
PUBMED: 27889185
PMCID: PMC5501282
DOI/URL:
Notes: Article -- Export Date: 3 January 2017 -- Source: Scopus
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MSK Authors
  1. James J Hsieh
    125 Hsieh
  2. Wenhuo Hu
    60 Hu
  3. Haiming Xu
    18 Xu
  4. Christopher Yongchul Park
    90 Park
  5. Scott Allen Armstrong
    108 Armstrong
  6. Chun-Wei Chen
    20 Chen
  7. Amit U Sinha
    13 Sinha
  8. Scott Haihua Chu
    7 Chu
  9. Richard Patrick Koche
    176 Koche
  10. Gerard Laurence Brien
    3 Brien
  11. Meghan Elizabeth Eisold
    3 Eisold