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急性髓系白血病患者的TP53突变与不良临床结局相关,无论一线诱导方案和异基因造血细胞移植情况如何。

TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation.

作者信息

Zhao Davidson, Zarif Mojgan, Zhou Qianghua, Capo-Chichi José-Mario, Schuh Andre, Minden Mark D, Atenafu Eshetu G, Kumar Rajat, Chang Hong

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Department of Laboratory Hematology, Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada.

出版信息

Cancers (Basel). 2023 Jun 16;15(12):3210. doi: 10.3390/cancers15123210.


DOI:10.3390/cancers15123210
PMID:37370821
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10296444/
Abstract

mutations are associated with extremely poor outcomes in acute myeloid leukemia (AML). The outcomes of patients with -mutated () AML after different frontline treatment modalities are not well established. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for AML; however, long-term outcomes among patients with AML after allo-HCT are dismal, and the benefit of allo-HCT remains controversial. We sought to evaluate the outcomes of patients with AML after treatment with different frontline induction therapies and allo-HCT. A total of 113 patients with AML were retrospectively evaluated. Patients with AML who received intensive or azacitidine-venetoclax induction had higher complete remission rates compared to patients treated with other hypomethylating-agent-based induction regimens. However, OS and EFS were not significantly different among the induction regimen groups. Allo-HCT was associated with improved OS and EFS among patients with AML; however, allo-HCT was not significantly associated with improved OS or EFS in time-dependent or landmark analysis. While the outcomes of all patients were generally poor irrespective of therapeutic strategy, transplanted patients with lower variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher VAF. Our study provides further evidence that the current standards of care for AML confer limited therapeutic benefit to patients with mutations.

摘要

突变与急性髓系白血病(AML)的极差预后相关。-突变()AML患者在不同一线治疗模式后的预后尚未明确。异基因造血细胞移植(allo-HCT)是AML一种潜在的治愈性治疗方法;然而,allo-HCT后AML患者的长期预后不佳,allo-HCT的益处仍存在争议。我们试图评估不同一线诱导治疗和allo-HCT治疗后AML患者的预后。共回顾性评估了113例AML患者。与接受其他基于低甲基化剂的诱导方案治疗的患者相比,接受强化或阿扎胞苷-维奈托克诱导的AML患者完全缓解率更高。然而,诱导方案组之间的总生存期(OS)和无事件生存期(EFS)无显著差异。allo-HCT与AML患者的OS和EFS改善相关;然而,在时间依赖性或标志性分析中,allo-HCT与OS或EFS改善无显著关联。尽管无论治疗策略如何,所有患者的预后总体较差,但诊断时变异等位基因频率(VAF)较低的移植患者比VAF较高的移植患者预后更好。我们的研究提供了进一步的证据,表明AML目前的治疗标准对携带突变的患者治疗益处有限。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/e7e5cfec1399/cancers-15-03210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/e4be798f45e2/cancers-15-03210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/eee78e51d286/cancers-15-03210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/d4ccc01eea98/cancers-15-03210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/e7e5cfec1399/cancers-15-03210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/e4be798f45e2/cancers-15-03210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/eee78e51d286/cancers-15-03210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/d4ccc01eea98/cancers-15-03210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db2/10296444/e7e5cfec1399/cancers-15-03210-g004.jpg

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引用本文的文献

[1]
Genomic Profile and Clinical Outcomes in Acute Myeloid Leukemia with Monosomal Karyotype.

Int J Mol Sci. 2025-6-18

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Venetoclax and hypomethylating agents versus induction chemotherapy for newly diagnosed acute myeloid leukemia patients: a systematic review and meta-analysis.

BMC Cancer. 2025-5-19

[3]
SOHO State of the Art Updates and Next Questions | Transplanting Hope: Managing Relapsed/Refractory AML.

Clin Lymphoma Myeloma Leuk. 2025-9

[4]
Tetrahydrobenzimidazole TMQ0153 targets OPA1 and restores drug sensitivity in AML via ROS-induced mitochondrial metabolic reprogramming.

J Exp Clin Cancer Res. 2025-4-7

[5]
Mutation dynamics from diagnosis to relapse in acute myeloid leukemia with chromosomal 7 deletions.

Leuk Lymphoma. 2025-7

[6]
Factors associated with survival following allogeneic transplantation for myeloid neoplasms harboring TP53 mutations.

Blood Adv. 2025-3-14

[7]
Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group.

Blood Cancer J. 2025-1-11

[8]
Chemotherapy resistance in acute myeloid leukemia is mediated by A20 suppression of spontaneous necroptosis.

Nat Commun. 2024-10-24

[9]
Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype.

Clin Epigenetics. 2024-9-11

[10]
Patients with -Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study.

Cancers (Basel). 2024-8-7

本文引用的文献

[1]
Safety and efficacy of CPX-351 in younger patients (<60 years old) with secondary acute myeloid leukemia.

Blood. 2023-3-23

[2]
Molecular characterization of AML-MRC reveals TP53 mutation as an adverse prognostic factor irrespective of MRC-defining criteria, TP53 allelic state, or TP53 variant allele frequency.

Cancer Med. 2023-3

[3]
TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Biology, Current Therapy, and Future Directions.

Cancer Discov. 2022-11-2

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Outcomes with allogeneic hematopoietic stem cell transplantation in TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis.

Leuk Lymphoma. 2022-12

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Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine.

Clin Cancer Res. 2022-12-15

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Histopathology. 2022-10

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Blood. 2022-9-22

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Blood. 2022-9-15

[9]
Additional cytogenetic features determine outcome in patients allografted for TP53 mutant acute myeloid leukemia.

Cancer. 2022-8-1

[10]
TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia.

Blood. 2022-7-7

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