TP53突变型急性髓系白血病中的突变模式
Patterns of mutations in TP53 mutated AML.
作者信息
Welch John S
机构信息
Department of Internal Medicine, Washington University, 660 Euclid Ave, Box 8007, St. Louis, MO 63110, USA.
出版信息
Best Pract Res Clin Haematol. 2018 Dec;31(4):379-383. doi: 10.1016/j.beha.2018.09.010. Epub 2018 Sep 20.
Abstract
TP53 mutated acute myeloid leukemia (AML) responds poorly to chemotherapy and has a short overall survival rate with a median of 5-9 months. Poor outcomes in TP53 mutated AML following chemotherapy have been observed and treatment options remain limited, although the presence of TP53 mutations alone should not be a barrier to therapy. Decitabine is emerging as an alternative treatment option for patients with TP53 mutated AML, although the agent has not been associated with deep molecular remissions and requires additional consolidation. The clinical and genomic characteristics of TP53 mutated AML are reviewed in this paper.
摘要
TP53基因发生突变的急性髓系白血病（AML）对化疗反应不佳，总生存率较低，中位生存期为5至9个月。尽管单独存在TP53突变不应成为治疗的障碍，但化疗后TP53基因发生突变的AML患者预后较差，且治疗选择仍然有限。地西他滨正在成为TP53基因发生突变的AML患者的一种替代治疗选择，尽管该药物尚未与深度分子缓解相关联，且需要额外的巩固治疗。本文对TP53基因发生突变的AML的临床和基因组特征进行了综述。
相似文献
1
Patterns of mutations in TP53 mutated AML.TP53突变型急性髓系白血病中的突变模式
Best Pract Res Clin Haematol. 2018 Dec;31(4):379-383. doi: 10.1016/j.beha.2018.09.010. Epub 2018 Sep 20.
2
Role of p53 in regulation of hematopoiesis in health and disease.p53 在健康和疾病中的造血作用。
Curr Opin Hematol. 2022 Jul 1;29(4):194-200. doi: 10.1097/MOH.0000000000000715. Epub 2022 Mar 7.
3
Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia.地西他滨治疗的急性髓系白血病患者中存在单体核型和 17p 染色体缺失或 TP53 突变。
Ann Hematol. 2020 Jul;99(7):1551-1560. doi: 10.1007/s00277-020-04082-7. Epub 2020 Jun 6.
4
TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes.TP53与地西他滨在急性髓系白血病和骨髓增生异常综合征中的应用
N Engl J Med. 2016 Nov 24;375(21):2023-2036. doi: 10.1056/NEJMoa1605949.
5
[Biological and clinical significance of TP53 mutations in myelodysplastic syndrome and acute myeloid leukemia].[骨髓增生异常综合征和急性髓系白血病中TP53突变的生物学及临床意义]
Rinsho Ketsueki. 2023;64(9):955-961. doi: 10.11406/rinketsu.64.955.
6
Decitabine treatment in 311 patients with acute myeloid leukemia: outcome and impact of mutations - a registry based analysis.311 例急性髓系白血病患者用去甲基化药物地西他滨治疗的结果和基因突变的影响：一项基于注册登记的分析。
Leuk Lymphoma. 2021 Jun;62(6):1432-1440. doi: 10.1080/10428194.2020.1864354. Epub 2021 Jan 5.
7
TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Biology, Current Therapy, and Future Directions.TP53 突变型骨髓增生异常综合征和急性髓系白血病：生物学、当前治疗和未来方向。
Cancer Discov. 2022 Nov 2;12(11):2516-2529. doi: 10.1158/2159-8290.CD-22-0332.
8
Clinical outcomes and characteristics of patients with -mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience.伴有-突变的急性髓系白血病或骨髓增生异常综合征患者的临床结局和特征：一项单中心经验。
Leuk Lymphoma. 2020 Sep;61(9):2180-2190. doi: 10.1080/10428194.2020.1759051. Epub 2020 May 2.
9
Acute myeloid leukemia or myelodysplastic syndrome with chromosome 17 abnormalities and long-term outcomes with or without hematopoietic stem cell transplantation.伴有 17 号染色体异常的急性髓系白血病或骨髓增生异常综合征，以及造血干细胞移植与否的长期预后。
Leuk Res. 2020 Aug;95:106402. doi: 10.1016/j.leukres.2020.106402. Epub 2020 Jun 18.
10
Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax.地西他滨联合维奈克拉治疗 TP53 突变急性髓系白血病的疗效。
Cancer. 2021 Oct 15;127(20):3772-3781. doi: 10.1002/cncr.33689. Epub 2021 Jul 13.
引用本文的文献
1
Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications.根据国际癌症研究机构（ICC）和世界卫生组织（WHO）第五版分类法诊断TP53突变型髓系疾病
Blood Adv. 2025 Feb 11;9(3):445-454. doi: 10.1182/bloodadvances.2024014140.
2
Acute Erythroid Leukemia Post-Chemo-Radiotherapy and Autologous Stem Cell Transplantation Due to Multiple Myeloma: Tracing the Paths to Leukemic Transformation.多发性骨髓瘤化疗放疗及自体干细胞移植后继发急性红细胞白血病：白血病转化的路径追踪。
Int J Mol Sci. 2024 Jul 22;25(14):8003. doi: 10.3390/ijms25148003.
3
Venetoclax therapy and emerging resistance mechanisms in acute myeloid leukaemia.维奈托克治疗急性髓系白血病及耐药机制的研究进展。
Cell Death Dis. 2024 Jun 12;15(6):413. doi: 10.1038/s41419-024-06810-7.
4
Genetic heterogeneity in p53-null leukemia increases transiently with spindle assembly checkpoint inhibition and is not rescued by p53.p53 缺失型白血病中的遗传异质性随纺锤体组装检查点抑制而短暂增加，且不能被 p53 挽救。
Chromosoma. 2024 Jan;133(1):77-92. doi: 10.1007/s00412-023-00800-y. Epub 2023 May 31.
5
Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia.急性髓系白血病免疫表型参数与分子改变之间的关联
Biomedicines. 2023 Apr 5;11(4):1098. doi: 10.3390/biomedicines11041098.
6
TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms.TP53 基因突变变异等位基因频率≥10%与治疗相关髓系肿瘤的不良预后相关。
Blood Cancer J. 2023 Apr 11;13(1):51. doi: 10.1038/s41408-023-00821-x.
7
Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis.初诊、未经治疗的 TP53 突变型急性髓系白血病的治疗结局：系统评价和荟萃分析。
J Hematol Oncol. 2023 Mar 6;16(1):19. doi: 10.1186/s13045-023-01417-5.
8
Extramedullary Myeloid Leukemia in the Setting of a Myeloproliferative Neoplasm.骨髓增殖性肿瘤背景下的髓外髓样白血病
J Med Cases. 2022 Nov;13(11):561-568. doi: 10.14740/jmc3996. Epub 2022 Nov 27.
9
Pharmacogenetics of Drug Metabolism: The Role of Gene Polymorphism in the Regulation of Doxorubicin Safety and Efficacy.药物代谢的药物遗传学：基因多态性在阿霉素安全性和有效性调控中的作用
Cancers (Basel). 2022 Nov 4;14(21):5436. doi: 10.3390/cancers14215436.
10
Biomarkers of related driver genes predict anti-tumor efficacy of immune checkpoint inhibitors.相关驱动基因的生物标志物可预测免疫检查点抑制剂的抗肿瘤疗效。
Front Immunol. 2022 Sep 15;13:995785. doi: 10.3389/fimmu.2022.995785. eCollection 2022.
本文引用的文献
1
Chromothripsis in acute myeloid leukemia: biological features and impact on survival.急性髓系白血病中的染色体重排：生物学特征及其对生存的影响。
Leukemia. 2018 Jul;32(7):1609-1620. doi: 10.1038/s41375-018-0035-y. Epub 2018 Feb 23.
2
Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: A subgroup analysis of the DACO-016 trial.地西他滨可提高新诊断的急性髓系白血病且具有单倍体核型的老年患者的缓解率并延长无进展生存期：DACO-016试验的亚组分析
Am J Hematol. 2018 May;93(5):E125-E127. doi: 10.1002/ajh.25062. Epub 2018 Feb 24.
3
Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential.细胞应激因素导致不同白血病潜能的造血克隆的扩增。
Nat Commun. 2018 Jan 31;9(1):455. doi: 10.1038/s41467-018-02858-0.
4
Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1.DNMT3A、U2AF1 和 EZH2 基因突变可识别 CR1 后预后不良的中危急性髓系白血病患者。
Blood Cancer J. 2018 Jan 10;8(1):4. doi: 10.1038/s41408-017-0040-9.
5
Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome.重新审视种系TP53突变携带者的肿瘤模式和外显率：李-弗劳梅尼综合征的时间阶段
Curr Opin Oncol. 2018 Jan;30(1):23-29. doi: 10.1097/CCO.0000000000000423.
6
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others.治疗性靶向 p53：所有突变体都平等，但有些突变体比其他突变体更平等。
Nat Rev Clin Oncol. 2018 Jan;15(1):13-30. doi: 10.1038/nrclinonc.2017.151. Epub 2017 Sep 26.
7
Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes.非血液系统恶性肿瘤患者治疗相关克隆性造血很常见，并与不良临床结局相关。
Cell Stem Cell. 2017 Sep 7;21(3):374-382.e4. doi: 10.1016/j.stem.2017.07.010. Epub 2017 Aug 10.
8
Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity.具有明显 p53 突变的肺肿瘤对 p53 靶向治疗有相似的反应，但表现出基因型特异性的他汀类药物敏感性。
Genes Dev. 2017 Jul 1;31(13):1339-1353. doi: 10.1101/gad.298463.117. Epub 2017 Aug 8.
9
Molecularly targeted therapies for p53-mutant cancers.针对p53突变癌症的分子靶向疗法。
Cell Mol Life Sci. 2017 Nov;74(22):4171-4187. doi: 10.1007/s00018-017-2575-0. Epub 2017 Jun 22.
10
Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy.癌症中的突变型p53：积累、功能获得与治疗
J Mol Biol. 2017 Jun 2;429(11):1595-1606. doi: 10.1016/j.jmb.2017.03.030. Epub 2017 Apr 6.
Zotero 插件