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Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development.突变型p53增强白血病起始细胞的自我更新能力，以促进白血病发展。
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2
Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL.缺失增强了 HSC 的自我更新，从而驱动 T-ALL 中的肿瘤起始和白血病干细胞活性。
Cancer Discov. 2019 Mar;9(3):436-451. doi: 10.1158/2159-8290.CD-18-1005. Epub 2018 Dec 19.
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Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal.白血病干细胞功能异质性建模：STAT5在白血病干细胞自我更新中的作用
Blood. 2009 Nov 5;114(19):3983-93. doi: 10.1182/blood-2009-06-227603. Epub 2009 Aug 10.
4
Leukemogenic potency of the novel FLT3-N676K mutant.新型FLT3-N676K突变体的致白血病潜能。
Ann Hematol. 2016 Apr;95(5):783-91. doi: 10.1007/s00277-016-2616-z. Epub 2016 Feb 19.
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FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia.FLT3 抑制通过 FOXO 上调 HDAC8，使 p53 失活，从而促进 FLT3-ITD+ 急性髓系白血病的维持。
Blood. 2020 Apr 23;135(17):1472-1483. doi: 10.1182/blood.2019003538.
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Mutated p53 Promotes the Symmetric Self-Renewal of Cisplatin-Resistant Lung Cancer Stem-Like Cells and Inhibits the Recruitment of Macrophages.突变型 p53 促进顺铂耐药肺癌干细胞样细胞的对称自我更新，并抑制巨噬细胞的募集。
J Immunol Res. 2019 Oct 31;2019:7478538. doi: 10.1155/2019/7478538. eCollection 2019.
7
Self-renewal of leukemia stem cells in Friend virus-induced erythroleukemia requires proviral insertional activation of Spi1 and hedgehog signaling but not mutation of p53.Friend 病毒诱导的红白血病中白血病干细胞的自我更新需要前病毒插入激活 Spi1 和 hedgehog 信号通路，但不依赖于 p53 基因突变。
Stem Cells. 2012 Feb;30(2):121-30. doi: 10.1002/stem.781.
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In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels.异常的MYB-GATA1融合蛋白的体内表达在GATA1水平降低的情况下会诱发白血病。
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A Gain-of-Function p53-Mutant Oncogene Promotes Cell Fate Plasticity and Myeloid Leukemia through the Pluripotency Factor FOXH1.抑癌基因 p53 功能获得性突变通过多能性因子 FOXH1 促进细胞命运可塑性和髓性白血病。
Cancer Discov. 2019 Jul;9(7):962-979. doi: 10.1158/2159-8290.CD-18-1391. Epub 2019 May 8.
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Loss of p53 induces leukemic transformation in a murine model of Jak2 V617F-driven polycythemia vera.p53 缺失导致 Jak2 V617F 驱动的真性红细胞增多症小鼠模型中的白血病转化。
Oncogene. 2017 Jun 8;36(23):3300-3311. doi: 10.1038/onc.2016.478. Epub 2017 Jan 9.

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Drug Resistance Mechanisms of Acute Myeloid Leukemia Stem Cells.急性髓系白血病干细胞的耐药机制
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5
Role of p53 in regulation of hematopoiesis in health and disease.p53 在健康和疾病中的造血作用。
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A unique role of p53 haploinsufficiency or loss in the development of acute myeloid leukemia with FLT3-ITD mutation.p53 杂合性缺失或丢失在伴有 FLT3-ITD 突变的急性髓系白血病中的独特作用。
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7
Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?造血在衰老过程中的命运。我们真正了解什么，以及它有什么影响？
Stem Cell Rev Rep. 2020 Dec;16(6):1020-1048. doi: 10.1007/s12015-020-10065-y. Epub 2020 Nov 3.
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Esophageal squamous cell cancer coincides with myelodysplastic syndrome/acute myelogenous leukemia: A case report and review of the literature.食管鳞状细胞癌合并骨髓增生异常综合征/急性髓系白血病：一例报告并文献复习
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9
AML chemoresistance: The role of mutant TP53 subclonal expansion and therapy strategy.急性髓系白血病化疗耐药：突变型 TP53 亚克隆扩增的作用及治疗策略。
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10
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.一线 venetoclax 联合治疗老年 AML 患者后的反应和治疗失败的分子模式。
Blood. 2020 Mar 12;135(11):791-803. doi: 10.1182/blood.2019003988.

本文引用的文献

1
Genotoxic stresses promote clonal expansion of hematopoietic stem cells expressing mutant p53.基因毒性应激促进表达突变型p53的造血干细胞的克隆性扩增。
Leukemia. 2018 Mar;32(3):850-854. doi: 10.1038/leu.2017.325. Epub 2017 Nov 16.
2
Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy.成人急性髓系白血病中p53蛋白的功能失调多样性：对诊断检查和治疗的启示
Blood. 2017 Aug 10;130(6):699-712. doi: 10.1182/blood-2017-02-763086. Epub 2017 Jun 12.
3
Molecular therapy for acute myeloid leukaemia.急性髓系白血病的分子治疗
Nat Rev Clin Oncol. 2016 May;13(5):305-18. doi: 10.1038/nrclinonc.2015.210. Epub 2015 Dec 1.
4
Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.初诊及复发时伴有FLT3-ITD的急性髓系白血病体细胞突变分析
Blood. 2015 Nov 26;126(22):2491-501. doi: 10.1182/blood-2015-05-646240. Epub 2015 Oct 5.
5
Drugging the p53 pathway: understanding the route to clinical efficacy.靶向 p53 通路：探索通往临床疗效的途径。
Nat Rev Drug Discov. 2014 Mar;13(3):217-36. doi: 10.1038/nrd4236.
6
ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia.ASXL1、TP53和IKZF3突变存在于慢性髓性白血病的慢性期和急变期。
Blood Cancer J. 2013 Nov 8;3(11):e157. doi: 10.1038/bcj.2013.54.
7
Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia.靶向 FMS 样酪氨酸激酶 3 治疗急性髓系白血病。
Leukemia. 2012 Oct;26(10):2176-85. doi: 10.1038/leu.2012.114. Epub 2012 Apr 27.
8
TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome.急性髓系白血病伴复杂核型中 TP53 改变与特定拷贝数改变、单体核型和不良预后相关。
Blood. 2012 Mar 1;119(9):2114-21. doi: 10.1182/blood-2011-08-375758. Epub 2011 Dec 20.
9
Targeting leukemic stem cells by breaking their dormancy.通过打破白血病干细胞休眠来靶向它们。
Mol Oncol. 2010 Oct;4(5):443-50. doi: 10.1016/j.molonc.2010.06.001. Epub 2010 Jun 9.
10
When mutants gain new powers: news from the mutant p53 field.当突变体获得新能力时：来自突变型p53领域的消息。
Nat Rev Cancer. 2009 Oct;9(10):701-13. doi: 10.1038/nrc2693. Epub 2009 Aug 20.

Mutant p53 enhances leukemia-initiating cell self-renewal to promote leukemia development.

作者信息

Nabinger Sarah C, Chen Sisi, Gao Rui, Yao Chonghua, Kobayashi Michihiro, Vemula Sasidhar, Fahey Aidan C, Wang Christine, Daniels Cecil, Boswell H Scott, Sandusky George E, Mayo Lindsey D, Kapur Reuben, Liu Yan

机构信息

Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

出版信息

Leukemia. 2019 Jun;33(6):1535-1539. doi: 10.1038/s41375-019-0377-0. Epub 2019 Jan 23.

DOI:10.1038/s41375-019-0377-0
PMID:30675010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9202234/
Abstract
摘要