دورية أكاديمية
IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia.
| العنوان: | IKAROS and CK2 regulate expression of BCL-XL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia. |
|---|---|
| المؤلفون: | Song C; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; Department of Medicine, Ohio State University College of Medicine, Columbus, OH., Ge Z; Department of Hematology and Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China., Ding Y; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Tan BH; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Desai D; Department of Pharmacology and., Gowda K; Department of Pharmacology and., Amin S; Department of Pharmacology and., Gowda R; Department of Pharmacology and., Robertson GP; Department of Pharmacology and., Yue F; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA., Huang S; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Spiegelman V; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Payne JL; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; Department of Basic Sciences and., Reeves ME; Department of Surgery, Loma Linda University College of Medicine, Loma Linda, CA., Gurel Z; Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI., Iyer S; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Dhanyamraju PK; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Xiang M; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; School of Pharmaceutical Science, South-Central University for Nationalities, Wuhan, China., Kawasawa YI; Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA., Cury NM; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; Graduate Program in Genetics and Molecular Biology, State University of Campinas, Campinas Sao Paulo, Brazil.; Laboratório de Biologia Molecular, Centro Infantil Boldrini, Campinas, Brazil., Yunes JA; Department of Molecular Biology, Centro Infantil Boldrini, State University of Campinas, Campinas, Brazil., McGrath M; Department of Pediatrics, University of Michigan, Ann Arbor, MI., Schramm J; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Su R; Department of Pathology and Human Anatomy, Loma Linda University College of Medicine, Loma Linda, CA., Yang Y; Department of Medicine, Ohio State University College of Medicine, Columbus, OH., Zhao Z; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; General Hospital of Ningxia Medical University, Yingchuan, China., Lyu X; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.; Renmin Hospital of Wuhan University, Wuhan, China; and., Muschen M; Department of Systems Biology, City of Hope Comprehensive Cancer Center, Monrovia, CA., Payne KJ; Department of Pathology and Human Anatomy, Loma Linda University College of Medicine, Loma Linda, CA., Gowda C; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA., Dovat S; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA. |
| المصدر: | Blood [Blood] 2020 Sep 24; Vol. 136 (13), pp. 1520-1534. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm* , Gene Expression Regulation, Leukemic*/drug effects, Casein Kinase II/*genetics , Ikaros Transcription Factor/*genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics , bcl-X Protein/*genetics, Animals ; Antibiotics, Antineoplastic/pharmacology ; Antibiotics, Antineoplastic/therapeutic use ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Humans ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy |
| مستخلص: | High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the IKAROS (encoded by the IKZF1 gene) tumor suppressor. Here, we report that IKAROS regulates expression of the BCL2L1 gene (encodes the BCL-XL protein) in human B-ALL. Gain-of-function and loss-of-function experiments demonstrate that IKAROS binds to the BCL2L1 promoter, recruits histone deacetylase HDAC1, and represses BCL2L1 expression via chromatin remodeling. In leukemia, IKAROS' function is impaired by oncogenic casein kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces IKAROS binding and recruitment of HDAC1 to the BCL2L1 promoter. This results in a loss of IKAROS-mediated repression of BCL2L1 and increased expression of BCL-XL. Increased expression of BCL-XL and/or CK2, as well as reduced IKAROS expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, increases binding of IKAROS to the BCL2L1 promoter and enhances IKAROS-mediated repression of BCL2L1 in B-ALL. Treatment with CX-4945 increases sensitivity to doxorubicin in B-ALL, and reverses resistance to doxorubicin in multidrug-resistant B-ALL. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia. These data lay the groundwork for clinical testing of a rationally designed, targeted therapy that combines the CK2 inhibitor, CX-4945, with doxorubicin for the treatment of hematopoietic malignancies. (© 2020 by The American Society of Hematology.) |
| References: | Cancer Cell. 2012 Aug 14;22(2):153-66. (PMID: 22897847) Br J Haematol. 2014 Apr;165(2):217-26. (PMID: 24467740) Haematologica. 2003 May;88(5):497-508. (PMID: 12745269) J Immunol. 1985 Mar;134(3):1524-30. (PMID: 3918103) Lancet. 2013 Jun 1;381(9881):1943-55. (PMID: 23523389) BMC Cancer. 2006 Aug 23;6:213. (PMID: 16928273) Blood. 1982 Dec;60(6):1305-9. (PMID: 6982733) J Biol Chem. 2003 Dec 19;278(51):50915-22. (PMID: 14559912) Leuk Res. 1993 Jun;17(6):491-9. (PMID: 8099376) J Exp Med. 1995 Sep 1;182(3):821-8. (PMID: 7650488) Leukemia. 2016 Jun;30(6):1436-40. (PMID: 26639180) Nature. 2005 Jun 2;435(7042):677-81. (PMID: 15902208) Int J Cancer. 2004 Jan 1;108(1):78-85. (PMID: 14618619) Cancer Sci. 2016 Jun;107(6):721-5. (PMID: 26991355) Cell. 1995 Oct 20;83(2):289-99. (PMID: 7585946) Cancer Res. 2010 Dec 15;70(24):10288-98. (PMID: 21159648) J Biol Chem. 2008 Mar 28;283(13):8291-300. (PMID: 18223295) Leukemia. 2015 Nov;29(11):2154-61. (PMID: 26050650) Leukemia. 2014 Feb;28(2):302-10. (PMID: 23823658) Epigenomics. 2018 Jan;10(1):59-69. (PMID: 28994305) Carcinogenesis. 2018 Mar 8;39(3):458-470. (PMID: 29329420) Clin Cancer Res. 2012 May 15;18(10):2754-67. (PMID: 22589484) Leukemia. 2017 Aug;31(8):1840-1842. (PMID: 28529312) Blood. 1997 Apr 15;89(8):2986-93. (PMID: 9108419) Expert Rev Hematol. 2009 Jun;2(3):297-303. (PMID: 21082971) Cancer Cell. 2006 Nov;10(5):389-99. (PMID: 17097561) Cell. 1993 Aug 27;74(4):597-608. (PMID: 8358789) Sci Rep. 2016 Nov 25;6:38004. (PMID: 27885263) J Biol Chem. 2009 May 15;284(20):13869-80. (PMID: 19282287) Clin Cancer Res. 2007 Feb 1;13(3):1019-28. (PMID: 17289898) J Clin Oncol. 2009 Feb 20;27(6):911-8. (PMID: 19124805) Haematologica. 2018 Apr;103(4):565-574. (PMID: 29519871) Oncogenesis. 2018 Nov 12;7(11):84. (PMID: 30420689) Mol Cell Biol. 1994 Dec;14(12):8292-303. (PMID: 7969165) Oncotarget. 2015 Nov 3;6(34):36113-25. (PMID: 26416351) Blood. 2004 Apr 1;103(7):2779-86. (PMID: 14656874) Int J Oncol. 2003 Jan;22(1):123-8. (PMID: 12469194) Leukemia. 2018 Jan;32(1):1-10. (PMID: 28951560) Biochem J. 2017 Oct 23;474(21):3643-3657. (PMID: 29061914) J Investig Med. 2016 Mar;64(3):735-9. (PMID: 26912004) Leuk Res. 2002 Mar;26(3):311-6. (PMID: 11792421) EMBO J. 1999 Jun 1;18(11):3090-100. (PMID: 10357820) Science. 1992 Oct 30;258(5083):808-12. (PMID: 1439790) Lancet Oncol. 2009 Feb;10(2):125-34. (PMID: 19138562) Leukemia. 2012 Oct;26(10):2204-11. (PMID: 22441210) Mol Cell Biochem. 2011 Oct;356(1-2):201-7. (PMID: 21750978) Mol Cell Biol. 1994 Nov;14(11):7111-23. (PMID: 7935426) N Engl J Med. 2015 Oct 15;373(16):1541-52. (PMID: 26465987) Genes Dev. 2000 Sep 1;14(17):2146-60. (PMID: 10970879) Leukemia. 2011 Feb;25(2):254-8. (PMID: 21102428) Blood. 2008 Nov 1;112(9):3847-55. (PMID: 18650450) Blood. 2011 Aug 11;118(6):1663-74. (PMID: 21673344) Oncotarget. 2017 Jan 31;8(5):8022-8034. (PMID: 28030830) Cancer Res. 2008 May 1;68(9):3421-8. (PMID: 18451170) Blood. 2009 Sep 3;114(10):2159-67. (PMID: 19589926) Haematologica. 2001 May;86(5):470-7. (PMID: 11410409) Cell. 1997 Dec 12;91(6):845-54. (PMID: 9413993) Haematologica. 2008 Dec;93(12):1814-21. (PMID: 18838475) Haematologica. 2014 Jun;99(6):1062-8. (PMID: 24561792) Leukemia. 2016 Jul;30(7):1599-603. (PMID: 26713593) Cancer Res. 1996 Oct 15;56(20):4743-8. (PMID: 8840993) Curr Pharm Des. 2017;23(1):95-107. (PMID: 27719640) Leuk Res. 2002 Dec;26(12):1119-23. (PMID: 12443885) Nat Genet. 2004 May;36(5):502-6. (PMID: 15098035) Adv Biol Regul. 2017 Jan;63:71-80. (PMID: 27666503) PLoS One. 2012;7(7):e40934. (PMID: 22848414) Blood. 2013 Oct 10;122(15):2622-9. (PMID: 23974192) J Virol. 1999 Oct;73(10):7981-7. (PMID: 10482545) J Clin Oncol. 2009 Nov 1;27(31):5202-7. (PMID: 19770381) Cell Mol Life Sci. 2018 Jun;75(11):2011-2026. (PMID: 29119230) Nat Rev Drug Discov. 2017 Apr;16(4):273-284. (PMID: 28209992) Pediatr Blood Cancer. 2011 Jun;56(6):984-93. (PMID: 21370430) Cancer. 2015 Aug 1;121(15):2517-28. (PMID: 25891003) Leukemia. 2010 Jul;24(7):1258-64. (PMID: 20445578) Br J Haematol. 2001 Mar;112(3):706-13. (PMID: 11260076) Cold Spring Harb Symp Quant Biol. 1999;64:79-86. (PMID: 11232340) Haematologica. 2013 Mar;98(3):428-32. (PMID: 22875627) Leukemia. 2007 Jun;21(6):1258-66. (PMID: 17443227) Blood. 2004 Nov 15;104(10):3028-37. (PMID: 15256423) JAMA Oncol. 2018 Oct 1;4(10):1413-1420. (PMID: 29931220) Blood. 2015 Oct 8;126(15):1813-22. (PMID: 26219304) J Clin Oncol. 2012 Feb 10;30(5):488-96. (PMID: 22184378) Br J Haematol. 2015 May;169(4):479-91. (PMID: 25753742) Haematologica. 2017 Mar;102(3):541-551. (PMID: 27979924) Blood. 2018 Sep 20;132(12):1248-1264. (PMID: 30012635) Mol Cell Biol. 1991 Oct;11(10):5229-43. (PMID: 1922043) Immunity. 1999 Mar;10(3):345-55. (PMID: 10204490) N Engl J Med. 2009 Jan 29;360(5):470-80. (PMID: 19129520) Cancer Discov. 2014 Sep;4(9):1074-87. (PMID: 24994123) Adv Exp Med Biol. 1996;406:75-82. (PMID: 8910673) Cancer Biol Ther. 2005 Jan;4(1):32-8. (PMID: 15684603) Blood. 1997 Aug 1;90(3):1208-16. (PMID: 9242554) Leukemia. 2019 Nov;33(11):2720-2731. (PMID: 31073152) J Immunol. 2009 Apr 1;182(7):4255-66. (PMID: 19299724) J Biol Chem. 2016 Feb 19;291(8):4004-18. (PMID: 26655717) Blood. 2010 Dec 2;116(23):4874-84. (PMID: 20699438) Mol Cell Biol. 2004 Apr;24(7):2797-807. (PMID: 15024069) Blood. 2015 Jun 25;125(26):3977-87. (PMID: 25999453) N Engl J Med. 2014 Sep 11;371(11):1005-15. (PMID: 25207766) |
| معلومات مُعتمدة: | R01 HL151195 United States HL NHLBI NIH HHS; R01 HG009906 United States HG NHGRI NIH HHS; R01 DK110108 United States DK NIDDK NIH HHS; R01 CA204044 United States CA NCI NIH HHS; KL2 TR002015 United States TR NCATS NIH HHS; F30 CA221109 United States CA NCI NIH HHS; R01 CA213912 United States CA NCI NIH HHS; R01 CA193167 United States CA NCI NIH HHS; UL1 TR002014 United States TR NCATS NIH HHS; R01 CA209829 United States CA NCI NIH HHS; R01 CA243167 United States CA NCI NIH HHS; R35 GM124820 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Antibiotics, Antineoplastic) 0 (BCL2L1 protein, human) 0 (IKZF1 protein, human) 0 (bcl-X Protein) 148971-36-2 (Ikaros Transcription Factor) 80168379AG (Doxorubicin) EC 2.7.11.1 (Casein Kinase II) |
| تواريخ الأحداث: | Date Created: 20200513 Date Completed: 20210322 Latest Revision: 20210610 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7515690 |
| DOI: | 10.1182/blood.2019002655 |
| PMID: | 32396934 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
|---|---|
| DOI: | 10.1182/blood.2019002655 |