دورية أكاديمية
أعرض في EDS

Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.

التفاصيل البيبلوغرافية
العنوان: Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.
المؤلفون: Rogers JH; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Stem Cells and Regenerative Medicine Center., Gupta R; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Department of Medicine., Reyes JM; Center for Cell and Gene Therapy.; Stem Cells and Regenerative Medicine Center.; Department of Molecular and Human Genetics.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX., Gundry MC; Center for Cell and Gene Therapy.; Stem Cells and Regenerative Medicine Center.; Department of Molecular and Human Genetics.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX., Medrano G; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Stem Cells and Regenerative Medicine Center., Guzman A; Center for Cell and Gene Therapy.; Stem Cells and Regenerative Medicine Center.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX., Aguilar R; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Center for Cell and Gene Therapy., Conneely SE; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX., Song T; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX., Johnson C; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX., Barnes S; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX., Cristobal CDD; Center for Cell and Gene Therapy.; Department of Molecular and Human Genetics., Kurtz K; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX., Brunetti L; Center for Cell and Gene Therapy.; Stem Cells and Regenerative Medicine Center.; Centro di Ricerca Emato-Oncologica, University of Perugia, Perugia, Italy; and., Goodell MA; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Stem Cells and Regenerative Medicine Center.; Department of Molecular and Human Genetics.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Rau RE; Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.; Center for Cell and Gene Therapy.
المصدر: Blood advances [Blood Adv] 2021 Oct 12; Vol. 5 (19), pp. 3876-3890.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Burkitt Lymphoma* , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma*/genetics, Animals ; Humans ; Ikaros Transcription Factor/genetics ; Mice ; Prognosis ; Recurrence
مستخلص: IKAROS family zinc finger 1 (IKZF1) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-cell acute lymphoblastic leukemia. Due to the heterogeneity of concomitant lesions, it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance, and whether their consideration as a prognostic indicator is valuable in improving outcome. CRISPR/Cas9 strategies were used to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment that can be linked to loss of IKAROS protein. IKZF1 knockout and heterozygous null cells displayed relative resistance to a number of common therapies for B-cell acute lymphoblastic leukemia, including dexamethasone, asparaginase, and daunorubicin. Transcription profiling revealed a stem/myeloid cell-like phenotype and JAK/STAT upregulation after IKAROS loss. A CRISPR homology-directed repair strategy was also used to knock-in the dominant-negative IK6 isoform into the endogenous locus, and a similar drug resistance profile, with the exception of retained dexamethasone sensitivity, was observed. Interestingly, IKZF1 knockout and IK6 knock-in cells both have significantly increased sensitivity to cytarabine, likely owing to marked downregulation of SAMHD1 after IKZF1 knockout. Both types of IKZF1 lesions decreased the survival time of xenograft mice, with higher numbers of circulating blasts and increased organ infiltration. Given these findings, exact specification of IKZF1 status in patients may be a beneficial addition to risk stratification and could inform therapy.
(© 2021 by The American Society of Hematology.)
References: Cancer Cell. 2018 Sep 10;34(3):499-512.e9. (PMID: 30205049)
Nat Immunol. 2014 Mar;15(3):294-304. (PMID: 24509510)
Leukemia. 2017 Aug;31(8):1840-1842. (PMID: 28529312)
Blood. 2020 Jan 23;135(4):252-260. (PMID: 31821407)
Cancer Res. 1999 Aug 15;59(16):3931-4. (PMID: 10463586)
Nature. 2007 Apr 12;446(7137):758-64. (PMID: 17344859)
Leukemia. 2016 Jul;30(7):1599-603. (PMID: 26713593)
PLoS One. 2012;7(7):e40934. (PMID: 22848414)
Immunity. 1996 Dec;5(6):537-49. (PMID: 8986714)
Leuk Lymphoma. 2018 May;59(5):1033-1050. (PMID: 28745565)
Leuk Lymphoma. 2008 Mar;49(3):596-7. (PMID: 18297542)
Nat Commun. 2020 Jun 23;11(1):3165. (PMID: 32576829)
Int J Hematol. 2008 Sep;88(2):209-211. (PMID: 18668307)
Pediatr Blood Cancer. 2013 Oct;60(10):1587-92. (PMID: 23804397)
Exp Hematol. 2015 Jul;43(7):514-23.e1-2. (PMID: 25951974)
Leukemia. 2015 Nov;29(11):2154-61. (PMID: 26050650)
Br J Haematol. 2005 Feb;128(3):310-7. (PMID: 15667532)
J Clin Oncol. 2012 May 10;30(14):1663-9. (PMID: 22412151)
Nucleic Acids Res. 2014 Dec 16;42(22):e168. (PMID: 25300484)
Nat Immunol. 2006 Apr;7(4):382-91. (PMID: 16518393)
Cell Rep. 2016 Oct 25;17(5):1453-1461. (PMID: 27783956)
J Clin Oncol. 2018 Apr 20;36(12):1240-1249. (PMID: 29498923)
J Clin Oncol. 2018 Sep 10;36(26):2726-2735. (PMID: 30044693)
Haematologica. 2013 Aug;98(8):1226-31. (PMID: 23585525)
EMBO J. 1996 Oct 1;15(19):5358-69. (PMID: 8895580)
Science. 2014 Jan 17;343(6168):301-5. (PMID: 24292625)
EMBO J. 1999 Jun 1;18(11):3090-100. (PMID: 10357820)
Science. 1992 Oct 30;258(5083):808-12. (PMID: 1439790)
Nat Med. 2017 Feb;23(2):250-255. (PMID: 27991919)
Leuk Lymphoma. 2008 May;49(5):965-73. (PMID: 18464116)
Nat Med. 2017 Feb;23(2):256-263. (PMID: 28067901)
Nat Commun. 2019 Aug 2;10(1):3475. (PMID: 31375673)
Cell. 1994 Oct 7;79(1):143-56. (PMID: 7923373)
Haematologica. 2017 Oct;102(10):1739-1747. (PMID: 28751559)
EMBO Mol Med. 2020 Mar 6;12(3):e10419. (PMID: 31950591)
Blood. 2008 Nov 1;112(9):3847-55. (PMID: 18650450)
Oncol Rep. 2014 Mar;31(3):1373-9. (PMID: 24402122)
Nat Methods. 2015 Oct;12(10):982-8. (PMID: 26322839)
Cancer Cell. 2015 Sep 14;28(3):343-56. (PMID: 26321221)
Cell Rep. 2015 May 19;11(7):1079-89. (PMID: 25959823)
Cancer Discov. 2021 May;11(5):1082-1099. (PMID: 33408242)
Blood. 2013 Oct 31;122(18):3149-59. (PMID: 24002445)
PLoS One. 2015 Jul 01;10(7):e0130756. (PMID: 26131904)
Am J Hematol. 2009 Dec;84(12):849-50. (PMID: 19844989)
J Pediatr Hematol Oncol. 2011 Aug;33(6):429-32. (PMID: 21792038)
Cancer Cell. 2018 May 14;33(5):937-948.e8. (PMID: 29681510)
Nature. 2017 Feb 23;542(7642):479-483. (PMID: 28192788)
Br J Haematol. 2015 May;169(4):479-91. (PMID: 25753742)
Mol Cell Biol. 1991 Oct;11(10):5229-43. (PMID: 1922043)
N Engl J Med. 2009 Jan 29;360(5):470-80. (PMID: 19129520)
Science. 2014 Jan 17;343(6168):305-9. (PMID: 24292623)
Pediatr Blood Cancer. 2014 Oct;61(10):1779-85. (PMID: 24976218)
Stem Cell Reports. 2014 Nov 11;3(5):841-57. (PMID: 25418728)
معلومات مُعتمدة: K08 CA201611 United States CA NCI NIH HHS; P30 CA016672 United States CA NCI NIH HHS; P30 CA125123 United States CA NCI NIH HHS; S10 RR024574 United States RR NCRR NIH HHS; K12 CA090433 United States CA NCI NIH HHS; S10 OD025251 United States OD NIH HHS
المشرفين على المادة: 0 (IKZF1 protein, human)
148971-36-2 (Ikaros Transcription Factor)
تواريخ الأحداث: Date Created: 20210907 Date Completed: 20211101 Latest Revision: 20211219
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8679666
DOI: 10.1182/bloodadvances.2020002408
PMID: 34492683
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2020002408