Abstract：
:Vitamin D (VD) is a known differentiating agent, but the role of VD receptor (VDR) is still incompletely described in acute myeloid leukemia (AML), whose treatment is based mostly on antimitotic chemotherapy. Here, we present an unexpected role of VDR in normal hematopoiesis and in leukemogenesis. Limited VDR expression is associated with impaired myeloid progenitor differentiation and is a new prognostic factor in AML. In mice, the lack of Vdr results in increased numbers of hematopoietic and leukemia stem cells and quiescent hematopoietic stem cells. In addition, malignant transformation of Vdr-/- cells results in myeloid differentiation block and increases self-renewal. Vdr promoter is methylated in AML as in CD34+ cells, and demethylating agents induce VDR expression. Association of VDR agonists with hypomethylating agents promotes leukemia stem cell exhaustion and decreases tumor burden in AML mouse models. Thus, Vdr functions as a regulator of stem cell homeostasis and leukemic propagation.
journal_name
Cell Repjournal_title
Cell reportsauthors
Paubelle E,Zylbersztejn F,Maciel TT,Carvalho C,Mupo A,Cheok M,Lieben L,Sujobert P,Decroocq J,Yokoyama A,Asnafi V,Macintyre E,Tamburini J,Bardet V,Castaigne S,Preudhomme C,Dombret H,Carmeliet G,Bouscary D,Ginzburg YZdoi
10.1016/j.celrep.2019.12.055subject
Has Abstractpub_date
2020-01-21 00:00:00pages
739-754.e4issue
3issn
2211-1247pii
S2211-1247(19)31712-7journal_volume
30pub_type
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