دورية أكاديمية
Mutant NPM1 Maintains the Leukemic State through HOX Expression.
| العنوان: | Mutant NPM1 Maintains the Leukemic State through HOX Expression. |
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| المؤلفون: | Brunetti L; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Gundry MC; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Sorcini D; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Guzman AG; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA., Huang YH; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA., Ramabadran R; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Gionfriddo I; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Mezzasoma F; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Milano F; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Nabet B; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA., Buckley DL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Kornblau SM; Department of Leukemia and Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX 77030, USA., Lin CY; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Sportoletti P; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Martelli MP; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Falini B; Centro di Ricerca Emato-Oncologica (CREO), University of Perugia, 06132 Perugia, Italy., Goodell MA; Stem Cell and Regenerative Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Texas Children's Hospital and Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: goodell@bcm.edu. |
| المصدر: | Cancer cell [Cancer Cell] 2018 Sep 10; Vol. 34 (3), pp. 499-512.e9. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Gene Expression Regulation, Leukemic*, Homeodomain Proteins/*metabolism , Leukemia, Myeloid, Acute/*genetics , Nuclear Proteins/*genetics, Aged ; Animals ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Down-Regulation ; Female ; Humans ; Hydrazines/pharmacology ; Karyopherins/antagonists & inhibitors ; Karyopherins/metabolism ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/pathology ; Mice ; Mutation ; Nuclear Proteins/metabolism ; Nucleophosmin ; Proteolysis ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear/metabolism ; Triazoles/pharmacology ; Xenograft Model Antitumor Assays ; Exportin 1 Protein |
| مستخلص: | NPM1 is the most frequently mutated gene in cytogenetically normal acute myeloid leukemia (AML). In AML cells, NPM1 mutations result in abnormal cytoplasmic localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c is required to maintain the leukemic state. Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation. Finally, we show that XPO1 inhibition relocalizes NPM1c to the nucleus, promotes differentiation of AML cells, and prolongs survival of Npm1-mutated leukemic mice. We describe an exquisite dependency of NPM1-mutant AML cells on NPM1c, providing the rationale for the use of nuclear export inhibitors in AML with mutated NPM1. (Copyright © 2018 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2018 Sep 10;34(3):355-357. (PMID: 30205041) |
| References: | Immunity. 1997 Jan;6(1):13-22. (PMID: 9052833) Nat Methods. 2015 Oct;12(10):963-965. (PMID: 26280331) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19081-6. (PMID: 16357205) Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91. (PMID: 24799436) Nature. 2005 Sep 1;437(7055):147-53. (PMID: 16007073) Blood. 2012 Aug 30;120(9):1765-73. (PMID: 22677130) Blood. 2011 Sep 15;118(11):3096-106. (PMID: 21719597) Leukemia. 2013 Sep;27(9):1917-20. (PMID: 23478666) Leukemia. 2005 Oct;19(10):1760-7. (PMID: 16079892) Cell Rep. 2016 Oct 18;17(4):1193-1205. (PMID: 27760321) Cell. 2002 Apr 5;109(1):29-37. (PMID: 11955444) J Clin Oncol. 2016 Dec;34(34):4142-4150. (PMID: 26926685) Cancer Cell. 2007 Oct;12(4):367-80. (PMID: 17936561) Cancer Cell. 2016 Dec 12;30(6):863-878. (PMID: 27889185) Mol Cell. 2014 Oct 23;56(2):219-231. (PMID: 25263595) Oncotarget. 2016 Mar 29;7(13):16581-92. (PMID: 26918731) Br J Haematol. 2013 Apr;161(1):117-27. (PMID: 23373539) Cell. 2017 Feb 23;168(5):890-903.e15. (PMID: 28162770) Blood. 2017 Jun 15;129(24):3165-3174. (PMID: 28336527) Blood. 2006 Jun 1;107(11):4514-23. (PMID: 16455950) Leukemia. 2008 Dec;22(12):2285-8. (PMID: 18563173) Nat Protoc. 2012 Sep;7(9):1728-40. (PMID: 22936215) Cell. 2013 Apr 11;153(2):307-19. (PMID: 23582322) Leukemia. 2009 Oct;23(10):1731-43. (PMID: 19516275) Nat Chem Biol. 2018 May;14(5):431-441. (PMID: 29581585) Leukemia. 2017 Apr;31(4):798-807. (PMID: 28111462) Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943) Leukemia. 2013 Nov;27(11):2248-51. (PMID: 23584564) Bioinformatics. 2010 Sep 1;26(17):2071-5. (PMID: 20663846) J Clin Oncol. 2016 Sep 10;34(26):3166-74. (PMID: 27458288) Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12223-7. (PMID: 7527557) J Hematol Oncol. 2014 Dec 05;7:85. (PMID: 25476752) Blood. 2015 May 28;125(22):3455-65. (PMID: 25795919) Cell Stem Cell. 2013 Oct 3;13(4):459-70. (PMID: 24094326) Nat Methods. 2015 Apr;12(4):357-60. (PMID: 25751142) Blood. 2016 Jan 7;127(1):29-41. (PMID: 26660431) Nat Biotechnol. 2011 Jan;29(1):24-6. (PMID: 21221095) Blood. 2005 Aug 1;106(3):899-902. (PMID: 15831697) Cancer Res. 2007 Jul 1;67(13):6230-7. (PMID: 17616680) Genome Biol. 2009;10(3):R25. (PMID: 19261174) Blood. 2013 Apr 25;121(17):3447-58. (PMID: 23435463) Nat Methods. 2015 Oct;12(10):982-8. (PMID: 26322839) Nat Protoc. 2012 Mar 01;7(3):562-78. (PMID: 22383036) Blood. 2002 Jul 1;100(1):238-45. (PMID: 12070033) Br J Haematol. 2015 Aug;170(3):305-22. (PMID: 25891481) Leukemia. 2015 Jun;29(6):1279-89. (PMID: 25600023) Nature. 2016 Feb 4;530(7588):57-62. (PMID: 26814967) Leukemia. 2013 Jan;27(1):66-74. (PMID: 22847027) Clin Cancer Res. 2017 Mar 15;23(6):1552-1563. (PMID: 27649553) Cell Rep. 2016 Oct 25;17(5):1453-1461. (PMID: 27783956) N Engl J Med. 2008 May 1;358(18):1909-18. (PMID: 18450602) N Engl J Med. 2016 Jun 9;374(23):2209-2221. (PMID: 27276561) Nat Methods. 2013 Dec;10(12):1213-8. (PMID: 24097267) Bioinformatics. 2011 Apr 1;27(7):1017-8. (PMID: 21330290) Blood. 2011 Dec 8;118(24):6247-57. (PMID: 21948299) Cell. 1997 Sep 19;90(6):1051-60. (PMID: 9323133) Oncogene. 2007 Oct 15;26(47):6766-76. (PMID: 17934484) Nat Rev Cancer. 2006 Jul;6(7):493-505. (PMID: 16794633) Blood. 2007 Feb 1;109(3):874-85. (PMID: 17008539) Cancer Discov. 2016 Oct;6(10):1166-1181. (PMID: 27535106) N Engl J Med. 2005 Jan 20;352(3):254-66. (PMID: 15659725) N Engl J Med. 2016 Feb 4;374(5):422-33. (PMID: 26789727) Blood. 2018 Feb 22;131(8):855-863. (PMID: 29203585) J Vis Exp. 2018 Apr 10;(134):. (PMID: 29708546) Elife. 2017 Sep 19;6:. (PMID: 28926338) Protein Eng Des Sel. 2004 Jun;17(6):527-36. (PMID: 15314210) Blood. 2017 Oct 26;130(17):1911-1922. (PMID: 28835438) Elife. 2016 Jan 07;5:e09540. (PMID: 26740045) Leuk Res. 2010 Feb;34(2):261-2. (PMID: 19854508) |
| معلومات مُعتمدة: | R01 CA215452 United States CA NCI NIH HHS; R56 DK092883 United States DK NIDDK NIH HHS; 740230 International ERC_ European Research Council; P30 CA125123 United States CA NCI NIH HHS; K00 CA222736 United States CA NCI NIH HHS; T32 DK060445 United States DK NIDDK NIH HHS; R01 CA183252 United States CA NCI NIH HHS; F31 DK113705 United States DK NIDDK NIH HHS; R01 DK092883 United States DK NIDDK NIH HHS; P30 CA016672 United States CA NCI NIH HHS; F99 CA222736 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: AML; CRISPR; HOX; MEIS1; NPM1; XPO1; acute myeloid leukemia; dTAG; nuclear export; selinexor |
| المشرفين على المادة: | 0 (Homeodomain Proteins) 0 (Hydrazines) 0 (Karyopherins) 0 (NPM1 protein, human) 0 (Npm1 protein, mouse) 0 (Nuclear Proteins) 0 (Receptors, Cytoplasmic and Nuclear) 0 (Triazoles) 117896-08-9 (Nucleophosmin) 31TZ62FO8F (selinexor) |
| تواريخ الأحداث: | Date Created: 20180912 Date Completed: 20190624 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6159911 |
| DOI: | 10.1016/j.ccell.2018.08.005 |
| PMID: | 30205049 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2018.08.005 |