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KIT 基因突变转录本水平在 t(8;21)急性髓系白血病微小残留病监测中的作用

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Beijing Hightrust Diagnostics, Co., Ltd, Beijing, China.

出版信息

Hematol Oncol. 2024 Mar;42(2):e3264. doi: 10.1002/hon.3264.

Abstract

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KIT (D816V/H/Y or N822K) were tested for KIT transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT -high (KIT_H) group and the KIT -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

摘要

除了 RUNX1::RUNX1T1 转录水平外,据报道,使用 KIT 突变(KIT)DNA 水平进行可测量残留疾病监测可预测 t(8;21)急性髓系白血病(AML)的复发。然而,KIT 转录水平的有用性仍然未知。对 52 例 KIT(D816V/H/Y 或 N822K)突变的 t(8;21)AML 患者在诊断时和治疗期间采集的 202 份骨髓样本进行 KIT 转录水平检测,采用数字聚合酶链反应。通过对每个时间点的缓解进行受试者工作特征曲线分析,确定 KIT 的个体最佳截止值,这些时间点包括:诊断时、达到完全缓解(CR)后、以及 1 疗程和 2 疗程巩固治疗后。使用截止值将患者分为 KIT-高(KIT_H)组和 KIT-低(KIT_L)组。与 KIT_L 患者相比,KIT_H 患者在 1 疗程巩固治疗(p=0.0040 和 0.021)和 2 疗程巩固治疗(p=0.018 和 0.011)后,无复发生存率(RFS)和总生存率(OS)显著降低,但在诊断时和 CR 后无差异。在 2 疗程巩固治疗后,RUNX1::RUNX1T1 转录水平降低<3 对数,是 RFS 和 OS 的独立不良预后因素。在 2 疗程巩固治疗后,RUNX1::RUNX1T1 转录水平降低>3 对数的 KIT_H 患者(11/45;24.4%)与 RUNX1::RUNX1T1 转录水平降低<3 对数的患者的 RFS 相似。在 2 疗程巩固治疗后联合检测 KIT 和 RUNX1::RUNX1T1 转录水平可能改善 KIT 突变的 t(8;21)AML 患者的风险分层。

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