NUP98-Fusion Proteins Interact With the NSL and MLL1 Complexes To Drive Leukemogenesis


Journal article


Haiming Xu, D. Valerio, Meghan E. Eisold, Amit U. Sinha, R. Koche, Wenhuo Hu, C. Chen, S. Chu, Gerard L. Brien, Christopher Y. Park, J. Hsieh, P. Ernst, Scott A. Armstrong
Cancer Cell, 2016

Semantic Scholar DOI PubMedCentral PubMed
Cite

Cite

APA   Click to copy
Xu, H., Valerio, D., Eisold, M. E., Sinha, A. U., Koche, R., Hu, W., … Armstrong, S. A. (2016). NUP98-Fusion Proteins Interact With the NSL and MLL1 Complexes To Drive Leukemogenesis. Cancer Cell.


Chicago/Turabian   Click to copy
Xu, Haiming, D. Valerio, Meghan E. Eisold, Amit U. Sinha, R. Koche, Wenhuo Hu, C. Chen, et al. “NUP98-Fusion Proteins Interact With the NSL and MLL1 Complexes To Drive Leukemogenesis.” Cancer Cell (2016).


MLA   Click to copy
Xu, Haiming, et al. “NUP98-Fusion Proteins Interact With the NSL and MLL1 Complexes To Drive Leukemogenesis.” Cancer Cell, 2016.


BibTeX   Click to copy

@article{haiming2016a,
  title = {NUP98-Fusion Proteins Interact With the NSL and MLL1 Complexes To Drive Leukemogenesis},
  year = {2016},
  journal = {Cancer Cell},
  author = {Xu, Haiming and Valerio, D. and Eisold, Meghan E. and Sinha, Amit U. and Koche, R. and Hu, Wenhuo and Chen, C. and Chu, S. and Brien, Gerard L. and Park, Christopher Y. and Hsieh, J. and Ernst, P. and Armstrong, Scott A.}
}

Abstract

Summary 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. ChIP-seq 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.