MLL-AF9- and HOXA9-mediated Acute Myeloid Leukemia Stem Cell Self-renewal Requires JMJD1C

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2016 Feb 16

PMID 26878175

Citations 51

Authors

Nan Zhu

Mo Chen

Rowena Eng

Joshua DeJong

Amit U Sinha

Noushin F Rahnamay

Richard Koche

Fatima Al-Shahrour

Janna C Minehart

Chun-Wei Chen

Aniruddha J Deshpande

Haiming Xu

S Haihua Chu

Benjamin L Ebert

Robert G Roeder

Scott A Armstrong

Affiliations

Soon will be listed here.

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.

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