Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow
Summary: 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 leukemog...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719317127 |
| id |
doaj-53df66dd75014af1bb8489c5bd9cd832 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Etienne Paubelle Florence Zylbersztejn Thiago Trovati Maciel Caroline Carvalho Annalisa Mupo Meyling Cheok Liesbet Lieben Pierre Sujobert Justine Decroocq Akihiko Yokoyama Vahid Asnafi Elizabeth Macintyre Jérôme Tamburini Valérie Bardet Sylvie Castaigne Claude Preudhomme Hervé Dombret Geert Carmeliet Didier Bouscary Yelena Z. Ginzburg Hughes de Thé Marc Benhamou Renato C. Monteiro George S. Vassiliou Olivier Hermine Ivan C. Moura |
| spellingShingle |
Etienne Paubelle Florence Zylbersztejn Thiago Trovati Maciel Caroline Carvalho Annalisa Mupo Meyling Cheok Liesbet Lieben Pierre Sujobert Justine Decroocq Akihiko Yokoyama Vahid Asnafi Elizabeth Macintyre Jérôme Tamburini Valérie Bardet Sylvie Castaigne Claude Preudhomme Hervé Dombret Geert Carmeliet Didier Bouscary Yelena Z. Ginzburg Hughes de Thé Marc Benhamou Renato C. Monteiro George S. Vassiliou Olivier Hermine Ivan C. Moura Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow Cell Reports |
| author_facet |
Etienne Paubelle Florence Zylbersztejn Thiago Trovati Maciel Caroline Carvalho Annalisa Mupo Meyling Cheok Liesbet Lieben Pierre Sujobert Justine Decroocq Akihiko Yokoyama Vahid Asnafi Elizabeth Macintyre Jérôme Tamburini Valérie Bardet Sylvie Castaigne Claude Preudhomme Hervé Dombret Geert Carmeliet Didier Bouscary Yelena Z. Ginzburg Hughes de Thé Marc Benhamou Renato C. Monteiro George S. Vassiliou Olivier Hermine Ivan C. Moura |
| author_sort |
Etienne Paubelle |
| title |
Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow |
| title_short |
Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow |
| title_full |
Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow |
| title_fullStr |
Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow |
| title_full_unstemmed |
Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow |
| title_sort |
vitamin d receptor controls cell stemness in acute myeloid leukemia and in normal bone marrow |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-01-01 |
| description |
Summary: 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. : Paubelle et al. show that targeting the vitamin D receptor has anti-leukemic activity by acting on cell differentiation and by decreasing stemness of AML cells. Keywords: acute myeloid leukemia, vitamin D receptor, leukemic stem cell |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719317127 |
| work_keys_str_mv |
AT etiennepaubelle vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT florencezylbersztejn vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT thiagotrovatimaciel vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT carolinecarvalho vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT annalisamupo vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT meylingcheok vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT liesbetlieben vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT pierresujobert vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT justinedecroocq vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT akihikoyokoyama vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT vahidasnafi vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT elizabethmacintyre vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT jerometamburini vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT valeriebardet vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT sylviecastaigne vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT claudepreudhomme vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT hervedombret vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT geertcarmeliet vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT didierbouscary vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT yelenazginzburg vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT hughesdethe vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT marcbenhamou vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT renatocmonteiro vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT georgesvassiliou vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT olivierhermine vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow AT ivancmoura vitamindreceptorcontrolscellstemnessinacutemyeloidleukemiaandinnormalbonemarrow |
| _version_ |
1724863888426532864 |
| spelling |
doaj-53df66dd75014af1bb8489c5bd9cd8322020-11-25T02:22:02ZengElsevierCell Reports2211-12472020-01-01303739754.e4Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone MarrowEtienne Paubelle0Florence Zylbersztejn1Thiago Trovati Maciel2Caroline Carvalho3Annalisa Mupo4Meyling Cheok5Liesbet Lieben6Pierre Sujobert7Justine Decroocq8Akihiko Yokoyama9Vahid Asnafi10Elizabeth Macintyre11Jérôme Tamburini12Valérie Bardet13Sylvie Castaigne14Claude Preudhomme15Hervé Dombret16Geert Carmeliet17Didier Bouscary18Yelena Z. Ginzburg19Hughes de Thé20Marc Benhamou21Renato C. Monteiro22George S. Vassiliou23Olivier Hermine24Ivan C. Moura25INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Department of Clinical Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 75015 Paris, France; Corresponding authorINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, FranceINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, FranceINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, FranceHaematological Cancer Genetics, Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton Cambridge CB10 1SA, UKCentre of Research Jean-Pierre Aubert, INSERM UMR 837, 59000 Lille, FranceLaboratory of Experimental Medicine and Endocrinology, KU Leuven 3000, BelgiumInstitut Cochin, Département d’Immuno-Hématologie, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, INSERM U1016 Paris, France; Université Paris Descartes, Faculté de Médecine Sorbonne Paris Cité, Paris, France; Equipe Labellisée Ligue Nationale Contre le Cancer (LNCC), Paris, FranceINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, FranceNational Cancer Center Research Institute, Chiba 277-8577, JapanDepartment of Biological Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 75015 Paris, FranceDepartment of Biological Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 75015 Paris, FranceInstitut Cochin, Département d’Immuno-Hématologie, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, INSERM U1016 Paris, France; Université Paris Descartes, Faculté de Médecine Sorbonne Paris Cité, Paris, France; Equipe Labellisée Ligue Nationale Contre le Cancer (LNCC), Paris, FranceINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, FranceDepartment of Hematology, Hôpital Mignot, 78150 Le Chesnay, FranceCentre of Research Jean-Pierre Aubert, INSERM UMR 837, 59000 Lille, FranceDepartment of Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, 75010 Paris, FranceLaboratory of Experimental Medicine and Endocrinology, KU Leuven 3000, BelgiumInstitut Cochin, Département d’Immuno-Hématologie, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, INSERM U1016 Paris, France; Université Paris Descartes, Faculté de Médecine Sorbonne Paris Cité, Paris, France; Equipe Labellisée Ligue Nationale Contre le Cancer (LNCC), Paris, FranceErythropoiesis Laboratory, LFKRI, New York Blood Center, New York, NY, USAMolecular Virology and Pathology, INSERM UMR 944, 75010 Paris, France; Molecular Virology and Pathology, CNRS 7212, 75010 Paris, FranceINSERM U1149, Center for Research on Inflammation, 75018 Paris, FranceINSERM U1149, Center for Research on Inflammation, 75018 Paris, FranceHaematological Cancer Genetics, Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton Cambridge CB10 1SA, UKINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Department of Clinical Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 75015 Paris, France; Laboratory of Excellence GR-Ex, 75015 Paris, France; Corresponding authorINSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Paris Descartes – Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, 75015 Paris, France; Laboratory of Excellence GR-Ex, 75015 Paris, FranceSummary: 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. : Paubelle et al. show that targeting the vitamin D receptor has anti-leukemic activity by acting on cell differentiation and by decreasing stemness of AML cells. Keywords: acute myeloid leukemia, vitamin D receptor, leukemic stem cellhttp://www.sciencedirect.com/science/article/pii/S2211124719317127 |