دورية أكاديمية
أعرض في EDS

Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia.

التفاصيل البيبلوغرافية
العنوان: Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia.
المؤلفون: Uckelmann HJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Kim SM; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Wong EM; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Hatton C; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Giovinazzo H; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Gadrey JY; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Krivtsov AV; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Rücker FG; Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany., Döhner K; Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany., McGeehan GM; Syndax Pharmaceuticals, Inc., Waltham, MA, USA., Levine RL; Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Bullinger L; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany., Vassiliou GS; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Wellcome Trust Sanger Institute, Cambridge, UK., Armstrong SA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA. scott_armstrong@dfci.harvard.edu.; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
المصدر: Science (New York, N.Y.) [Science] 2020 Jan 31; Vol. 367 (6477), pp. 586-590.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
أسماء مطبوعة: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
مواضيع طبية MeSH: Genetic Therapy/*methods , Leukemia, Experimental/*prevention & control , Leukemia, Myeloid, Acute/*prevention & control , Nuclear Proteins/*genetics , Preleukemia/*therapy, Animals ; Chromatin/metabolism ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA Methyltransferase 3A ; Gene Knock-In Techniques ; Histone-Lysine N-Methyltransferase/metabolism ; Leukemia, Experimental/genetics ; Leukemia, Myeloid, Acute/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mutation ; Myeloid Progenitor Cells/pathology ; Myeloid-Lymphoid Leukemia Protein/metabolism ; Nucleophosmin ; Preleukemia/genetics ; Preleukemia/pathology ; Proto-Oncogene Proteins/metabolism
مستخلص: The initiating mutations that contribute to cancer development are sometimes present in premalignant cells. Whether therapies targeting these mutations can eradicate premalignant cells is unclear. Acute myeloid leukemia (AML) is an attractive system for investigating the effect of preventative treatment because this disease is often preceded by a premalignant state (clonal hematopoiesis or myelodysplastic syndrome). In Npm1c/Dnmt3a mutant knock-in mice, a model of AML development, leukemia is preceded by a period of extended myeloid progenitor cell proliferation and self-renewal. We found that this self-renewal can be reversed by oral administration of a small molecule (VTP-50469) that targets the MLL1-Menin chromatin complex. These preclinical results support the hypothesis that individuals at high risk of developing AML might benefit from targeted epigenetic therapy in a preventative setting.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
التعليقات: Comment in: Cancer Discov. 2020 Mar;10(3):341. (PMID: 32033969)
References: Cancer Cell. 2018 Sep 10;34(3):499-512.e9. (PMID: 30205049)
N Engl J Med. 2014 Dec 25;371(26):2477-87. (PMID: 25426838)
Cancer Cell. 2015 Apr 13;27(4):589-602. (PMID: 25817203)
Cancer Res. 2016 Feb 1;76(3):619-29. (PMID: 26747896)
Blood. 2017 Oct 26;130(17):1911-1922. (PMID: 28835438)
N Engl J Med. 2013 May 30;368(22):2059-74. (PMID: 23634996)
Nat Med. 2014 Dec;20(12):1472-8. (PMID: 25326804)
N Engl J Med. 2014 Dec 25;371(26):2488-98. (PMID: 25426837)
Nature. 2018 Jul;559(7714):400-404. (PMID: 29988082)
Nat Med. 2018 Jul;24(7):1015-1023. (PMID: 29988143)
Blood. 2013 Feb 21;121(8):1422-31. (PMID: 23264595)
Nat Med. 2016 Dec;22(12):1488-1495. (PMID: 27841873)
Mol Cell Biol. 2006 May;26(10):3902-16. (PMID: 16648484)
N Engl J Med. 2016 Jun 9;374(23):2209-2221. (PMID: 27276561)
Cancer Discov. 2016 Oct;6(10):1166-1181. (PMID: 27535106)
Nature. 2014 Feb 20;506(7488):328-33. (PMID: 24522528)
N Engl J Med. 2008 May 1;358(18):1909-18. (PMID: 18450602)
N Engl J Med. 2015 Sep 17;373(12):1136-52. (PMID: 26376137)
Cancer Cell. 2019 Dec 9;36(6):660-673.e11. (PMID: 31821784)
Leukemia. 2019 Jul;33(7):1635-1649. (PMID: 30692594)
Nat Genet. 2011 May;43(5):470-5. (PMID: 21441929)
N Engl J Med. 2005 Jan 20;352(3):254-66. (PMID: 15659725)
Nat Chem Biol. 2012 Jan 29;8(3):277-84. (PMID: 22286128)
Cell Rep. 2015 Mar 3;10(8):1239-45. (PMID: 25732814)
معلومات مُعتمدة: MC_PC_12009 United Kingdom MRC_ Medical Research Council; P50 CA206963 United States CA NCI NIH HHS; 23015 United Kingdom CRUK_ Cancer Research UK; P30 CA008748 United States CA NCI NIH HHS; R35 CA197594 United States CA NCI NIH HHS; R01 CA176745 United States CA NCI NIH HHS; R01 CA092660 United States CA NCI NIH HHS; MC_PC_17230 United Kingdom MRC_ Medical Research Council; U54 OD020355 United States OD NIH HHS; R01 CA204639 United States CA NCI NIH HHS; P01 CA066996 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Chromatin)
0 (Dnmt3a protein, mouse)
0 (Men1 protein, mouse)
0 (Npm1 protein, mouse)
0 (Nuclear Proteins)
0 (Proto-Oncogene Proteins)
117896-08-9 (Nucleophosmin)
149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
EC 2.1.1.37 (DNA Methyltransferase 3A)
EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
EC 2.1.1.43 (Kmt2a protein, mouse)
تواريخ الأحداث: Date Created: 20200201 Date Completed: 20200408 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC7754791
DOI: 10.1126/science.aax5863
PMID: 32001657
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-9203
DOI:10.1126/science.aax5863