scholarly journals Resistance to 1,25D-induced differentiation in human acute myeloid leukemia HL60-40AF cells is associated with reduced transcriptional activity and nuclear localization of the vitamin D receptor

2007 ◽  
Vol 213 (3) ◽  
pp. 816-825 ◽  
Author(s):  
Edward Garay ◽  
Robert Donnelly ◽  
Xuening Wang ◽  
George P. Studzinski
Keyword(s):  
Vitamin D ◽  
Acute Myeloid Leukemia ◽  
Nuclear Localization ◽  
Vitamin D Receptor ◽  
Myeloid Leukemia ◽  
Transcriptional Activity ◽  
Induced Differentiation ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Rina Wassermann ◽  
Victoria Novik ◽  
Michael Danilenko
Keyword(s):  
Vitamin D ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
U937 Cells ◽  
Differential Modulation ◽  
Cell Type ◽  
Induced Differentiation ◽  
Response Element ◽  
Cell Type Specific ◽  
Acute Myeloid

Plant polyphenols have been shown to enhance the differentiation of acute myeloid leukemia (AML) cells induced by the hormonal form of vitamin D3 (1α,25-dihydroxyvitamin D3; 1,25D). However, how these agents modulate 1,25D effects in different subtypes of AML cells remains poorly understood. Here, we show that both carnosic acid (CA) and silibinin (SIL) synergistically enhancd 1,25D-induced differentiation of myeloblastic HL60 cells. However, in promonocytic U937 cells, only CA caused potentiation while SIL attenuated 1,25D effect. The enhanced effect of 1,25D+CA was accompanied by increases in both the vitamin D receptor (VDR) and retinoid X receptor alpha (RXRα) protein levels and vitamin D response element (VDRE) transactivation in both cell lines. Similar increases were observed in HL60 cells treated with 1,25D + SIL. In U937 cells, however, SIL inhibited 1,25D-induced VDRE transactivation concomitant with downregulation of RXRα at both transcriptional and posttranscriptional levels. These inhibitory effects correlated with the inability of SIL, with or without 1,25D, to activate the Nrf2/antioxidant response element signaling pathway in U937 cells. These results suggest that opposite effects of SIL on 1,25D-induced differentiation of HL60 and U937 cells may be determined by cell-type-specific signaling and transcriptional responses to this polyphenol resulting in differential modulation of RXRα expression.

scholarly journals Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5243
Author(s):  
Marie Sabatier ◽  
Emeline Boet ◽  
Sonia Zaghdoudi ◽  
Nathan Guiraud ◽  
Alexis Hucteau ◽  
...  
Keyword(s):  
Vitamin D ◽  
Acute Myeloid Leukemia ◽  
Vitamin D Receptor ◽  
Myeloid Leukemia ◽  
Dependent Manner ◽  
Cooperative Effects ◽  
Idh Mutations ◽  
Transcriptional Changes ◽  
Acute Myeloid

Relapses and resistance to therapeutic agents are major barriers in the treatment of acute myeloid leukemia (AML) patients. These unfavorable outcomes emphasize the need for new strategies targeting drug-resistant cells. As IDH mutations are present in the preleukemic stem cells and systematically conserved at relapse, targeting IDH mutant cells could be essential to achieve a long-term remission in the IDH mutant AML subgroup. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutations, we showed that the production of an oncometabolite (R)-2-HG by IDH mutant enzymes induces vitamin D receptor-related transcriptional changes, priming these AML cells to differentiate with pharmacological doses of ATRA and/or VD. This activation occurs in a CEBPα-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutations and the vitamin D receptor pathway on differentiation in AML, revealing a novel therapeutic approach easily transferable/immediately applicable to this subgroup of AML patients.

scholarly journals Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow

Cell Reports ◽  
2020 ◽  
Vol 30 (3) ◽  
pp. 739-754.e4 ◽  
Author(s):  
Etienne Paubelle ◽  
Florence Zylbersztejn ◽  
Thiago Trovati Maciel ◽  
Caroline Carvalho ◽  
Annalisa Mupo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Acute Myeloid Leukemia ◽  
Vitamin D Receptor ◽  
Myeloid Leukemia ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Acute Myeloid
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