دورية أكاديمية
CBP Modulates Sensitivity to Dasatinib in Pre-BCR + Acute Lymphoblastic Leukemia.
| العنوان: | CBP Modulates Sensitivity to Dasatinib in Pre-BCR + Acute Lymphoblastic Leukemia. |
|---|---|
| المؤلفون: | Duque-Afonso J; Department of Pathology, Stanford University School of Medicine, Stanford, California.; Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany., Lin CH; Department of Pathology, Stanford University School of Medicine, Stanford, California., Han K; Department of Genetics, Stanford University School of Medicine, Stanford, California., Morgens DW; Department of Genetics, Stanford University School of Medicine, Stanford, California., Jeng EE; Department of Genetics, Stanford University School of Medicine, Stanford, California., Weng Z; Department of Pathology, Stanford University School of Medicine, Stanford, California.; Stanford Center for Genomics and Personalized Medicine, Stanford, California., Jeong J; Department of Pathology, Stanford University School of Medicine, Stanford, California., Wong SHK; Department of Pathology, Stanford University School of Medicine, Stanford, California., Zhu L; Department of Pathology, Stanford University School of Medicine, Stanford, California., Wei MC; Department of Pediatrics, Stanford University School of Medicine, Stanford, California., Chae HD; Department of Pediatrics, Stanford University School of Medicine, Stanford, California., Schrappe M; Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany., Cario G; Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany., Duyster J; Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany., Xiao X; Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon., Sakamoto KM; Department of Pediatrics, Stanford University School of Medicine, Stanford, California., Bassik MC; Department of Genetics, Stanford University School of Medicine, Stanford, California., Cleary ML; Department of Pathology, Stanford University School of Medicine, Stanford, California. mcleary@stanford.edu. |
| المصدر: | Cancer research [Cancer Res] 2018 Nov 15; Vol. 78 (22), pp. 6497-6508. Date of Electronic Publication: 2018 Sep 27. |
| 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: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm*, Antineoplastic Agents/*pharmacology , CREB-Binding Protein/*metabolism , Dasatinib/*pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy , Protein Kinase Inhibitors/*pharmacology, Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Protein Binding ; Protein Domains ; Pyrimidines/pharmacology ; RNA, Small Interfering/metabolism ; Signal Transduction ; Transcription, Genetic ; beta Catenin/genetics |
| مستخلص: | Dasatinib is a multi-tyrosine kinase inhibitor approved for treatment of Ph + acute lymphoblastic leukemia (ALL), but its efficacy is limited by resistance. Recent preclinical studies suggest that dasatinib may be a candidate therapy in additional ALL subtypes including pre-BCR + ALL. Here we utilized shRNA library screening and global transcriptomic analysis to identify several novel genes and pathways that may enhance dasatinib efficacy or mitigate potential resistance in human pre-BCR + ALL. Depletion of the transcriptional coactivator CBP increased dasatinib sensitivity by downregulating transcription of the pre-BCR signaling pathway previously associated with dasatinib sensitivity. Acquired resistance was due, in part, to upregulation of alternative pathways including WNT through a mechanism, suggesting transcriptional plasticity. Small molecules that disrupt CBP interactions with the CREB KID domain or β-catenin showed promising preclinical efficacy in combination with dasatinib. These findings highlight novel modulators of sensitivity to targeted therapies in human pre-BCR + ALL, which can be reversed by small-molecule inhibitors. They also identify promising therapeutic approaches to ameliorate dasatinib sensitivity and prevent resistance in ALL. Significance: These findings reveal mechanisms that modulate sensitivity to dasatinib and suggest therapeutic strategies to improve the outcome of patients with acute lymphoblastic leukemia. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6497/F1.large.jpg Cancer Res; 78(22); 6497-508. ©2018 AACR . (©2018 American Association for Cancer Research.) |
| References: | N Engl J Med. 2006 Jun 15;354(24):2531-41. (PMID: 16775234) Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):261-9. (PMID: 3455845) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7. (PMID: 15314234) Nature. 2011 Mar 10;471(7337):189-95. (PMID: 21390126) Nat Biotechnol. 2011 Oct 30;29(11):1046-51. (PMID: 22037378) Cancer Cell. 2012 Nov 13;22(5):656-67. (PMID: 23153538) J Med Chem. 2004 Dec 30;47(27):6658-61. (PMID: 15615512) Nat Rev Clin Oncol. 2015 Jun;12(6):344-57. (PMID: 25781572) Leukemia. 2016 Dec;30(12):2302-2311. (PMID: 27211267) Lancet. 2008 Mar 22;371(9617):1030-43. (PMID: 18358930) Nucleic Acids Res. 2014 Dec 16;42(22):e168. (PMID: 25300484) Cancer Cell. 2013 Oct 14;24(4):423-37. (PMID: 24054986) Nat Genet. 2015 Sep;47(9):1020-1029. (PMID: 26214592) Cancer Cell. 2015 Mar 9;27(3):409-25. (PMID: 25759025) Genome Res. 2012 Mar;22(3):568-76. (PMID: 22300766) Nature. 2011 Mar 10;471(7337):235-9. (PMID: 21390130) Nature. 2011 May 19;473(7347):384-8. (PMID: 21593872) Cell. 2013 Feb 14;152(4):909-22. (PMID: 23394947) Front Oncol. 2014 Mar 25;4:54. (PMID: 24724051) Nature. 2015 Sep 24;525(7570):543-547. (PMID: 26367798) Blood. 2015 May 7;125(19):2968-73. (PMID: 25712988) Clin Cancer Res. 2008 Jan 15;14(2):352-9. (PMID: 18223208) Cancer Discov. 2017 Mar;7(3):322-337. (PMID: 28069569) J Clin Invest. 2015 Sep;125(9):3667-80. (PMID: 26301816) Chem Biol. 2013 Nov 21;20(11):1352-63. (PMID: 24183972) Nat Commun. 2015 Mar 19;6:6604. (PMID: 25790293) Cell. 2009 May 29;137(5):835-48. (PMID: 19490893) Oncogene. 2009 Jun 11;28(23):2245-56. (PMID: 19421142) Nature. 2015 Sep 24;525(7570):538-42. (PMID: 26367796) Lancet. 2013 Jun 1;381(9881):1943-55. (PMID: 23523389) Leukemia. 2017 Jan;31(1):51-57. (PMID: 27461063) Nat Med. 2014 Oct;20(10):1138-46. (PMID: 25216638) Cancer Res. 2016 Dec 1;76(23):6937-6949. (PMID: 27758892) Nat Biotechnol. 2011 Jan;29(1):24-6. (PMID: 21221095) Cell. 2008 Apr 18;133(2):340-53. (PMID: 18423204) Blood. 2015 Oct 1;126(14):1683-94. (PMID: 26311362) Fly (Austin). 2012 Apr-Jun;6(2):80-92. (PMID: 22728672) Oncogene. 2014 Apr 24;33(17):2169-78. (PMID: 23728349) Cancer Cell. 2015 Aug 10;28(2):198-209. (PMID: 26190263) Cancer Cell. 2002 Aug;2(2):117-25. (PMID: 12204532) Nat Biotechnol. 2016 Jun;34(6):634-6. (PMID: 27159373) Nat Protoc. 2009;4(1):44-57. (PMID: 19131956) J Clin Oncol. 2011 Feb 10;29(5):532-43. (PMID: 21220592) Cell. 2014 Oct 23;159(3):647-61. (PMID: 25307932) J Cell Biol. 2000 Apr 17;149(2):249-54. (PMID: 10769018) Nat Genet. 2014 Apr;46(4):364-70. (PMID: 24584072) J Biol Chem. 2001 Apr 27;276(17):13505-8. (PMID: 11279224) Leukemia. 2016 Jun;30(6):1246-54. (PMID: 26847027) |
| معلومات مُعتمدة: | R01 CA214888 United States CA NCI NIH HHS; UL1 TR001085 United States TR NCATS NIH HHS |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (CTNNB1 protein, human) 0 (Protein Kinase Inhibitors) 0 (Pyrimidines) 0 (RNA, Small Interfering) 0 (beta Catenin) EC 2.3.1.48 (CREB-Binding Protein) EC 2.3.1.48 (CREBBP protein, human) RBZ1571X5H (Dasatinib) |
| تواريخ الأحداث: | Date Created: 20180929 Date Completed: 20191007 Latest Revision: 20240610 |
| رمز التحديث: | 20240610 |
| مُعرف محوري في PubMed: | PMC6283070 |
| DOI: | 10.1158/0008-5472.CAN-18-1703 |
| PMID: | 30262461 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
|---|---|
| DOI: | 10.1158/0008-5472.CAN-18-1703 |