MLL-AF9-and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C Journal Article

Authors: Zhu, N.; Chen, M.; Eng, R.; DeJong, J.; Sinha, A. U.; Rahnamay, N. F.; Koche, R.; Al-Shahrour, F.; Minehart, J. C.; Chen, C. W.; Deshpande, A. J.; Xu, H.; Chu, S. H.; Ebert, B. L.; Roeder, R. G.; Armstrong, S. A.
Article Title: MLL-AF9-and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C
Abstract: Self-renewal is a hallmark of both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opportunities that are more effective and less toxic than current treatments. Here, we employed an in vivo shRNA screen and identified jumonji domain-containing protein JMJD1C as an important driver of MLL-AF9 leukemia. Using a conditional mouse model, we showed that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9-and homeobox A9-driven (HOXA9-driven) leukemias. We determined that JMJD1C directly interacts with HOXA9 and modulates a HOXA9-controlled gene-expression program. In contrast, loss of JMJD1C led to only minor defects in blood homeostasis and modest effects on HSC self-renewal. Together, these data establish JMJD1C as an important mediator of MLL-AF9-and HOXA9-driven LSC function that is largely dispensable for HSC function.
Journal Title: Journal of Clinical Investigation
Volume: 126
Issue: 3
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation  
Date Published: 2016-03-01
Start Page: 997
End Page: 1011
Language: English
DOI: 10.1172/jci82978
PROVIDER: scopus
PMCID: PMC4767347
PUBMED: 26878175
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Haiming Xu
    18 Xu
  2. Scott Allen Armstrong
    108 Armstrong
  3. Chun-Wei Chen
    19 Chen
  4. Amit U Sinha
    13 Sinha
  5. Rowena Eng
    4 Eng
  6. Scott Haihua Chu
    7 Chu
  7. Nan Zhu
    9 Zhu
  8. Richard Patrick Koche
    124 Koche
  9. Mo   Chen
    1 Chen