伴有原始细胞过多的急性髓系白血病和骨髓增生异常综合征中突变型 TP53 的分子特征及预后

Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts.

机构信息

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, People's Republic of China.

Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, People's Republic of China.

出版信息

Int J Lab Hematol. 2023 Jun;45(3):344-352. doi: 10.1111/ijlh.14030. Epub 2023 Mar 1.

DOI:10.1111/ijlh.14030

PMID:36860196

Abstract

INTRODUCTION

Myeloid tumors typically harbor TP53 mutations, which are linked to a dismal prognosis. There are fewer studies on whether TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB) differ in molecular characteristics and should be considered as separate entities.

METHODS

Between January 2016 and December 2021, a retrospective analysis was done on a total of 73 newly diagnosed AML patients and 61 MDS-EB patients from the first affiliated hospital of Soochow University. We described a survival profile and a thorough characterization of newly found TP53-mutant AML and MDS-EB and investigated the relationship between these characteristics and overall survival (OS).

RESULTS

38 (31.1%) were mono-allelic, and 84 (68.9%) were bi-allelic. There is no significant difference between TP53-mutated AML and MDS-EB (median OS 12.9 verse 14.4 months; p = .558). Better overall survival was linked to mono-allelic TP53 than bi-allelic TP53(HR = 3.030, CI:1.714-5.354, p < .001). However, the number of TP53 mutations and comutations were not significantly associated with OS. TP53 variant allele frequency cutoff of 50% is significant correlation with OS (HR: 2.177, 95% CI: 1.142-4.148; p = .0063).

CONCLUSION

Our data revealed that allele status and allogeneic hematopoietic stem cell transplant independently affect the prognostic of AML and MDS-EB patients, with a concordance of molecular features and survival between these two disease entities. Our analysis favors considering TP53-mutated AML/MDS-EB as a distinct disorder.

摘要

简介

髓系肿瘤通常存在 TP53 突变，这与预后不良有关。关于是否存在不同的分子特征，以及是否应将 TP53 突变型急性髓系白血病（AML）和伴过多原始细胞的骨髓增生异常综合征（MDS-EB）视为两种不同的实体，相关研究较少。

方法

本研究回顾性分析了 2016 年 1 月至 2021 年 12 月苏州大学第一附属医院收治的 73 例新诊断 AML 患者和 61 例 MDS-EB 患者。我们描述了新发现的 TP53 突变型 AML 和 MDS-EB 的生存情况和全面特征，并探讨了这些特征与总生存（OS）的关系。

结果

38 例（31.1%）为单等位基因突变，84 例（68.9%）为双等位基因突变。TP53 突变型 AML 和 MDS-EB 之间无显著差异（中位 OS 12.9 个月与 14.4 个月；p=0.558）。与双等位基因突变相比，单等位基因突变的总生存更好（HR=3.030，CI：1.714-5.354，p<0.001）。然而，TP53 突变的数量和共突变与 OS 无显著相关性。TP53 变异等位基因频率截断值为 50%与 OS 显著相关（HR：2.177，95%CI：1.142-4.148；p=0.0063）。