Department of Hematology, Zhejiang Hospital, Hangzhou, China.
Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Int J Lab Hematol. 2019 Aug;41(4):485-492. doi: 10.1111/ijlh.13030. Epub 2019 May 17.
Cytogenetics and molecular testings for disease classifying and prognosis estimation are becoming routine in clinical practice. However, the molecular characteristics of acute monocytic leukemia (AML-M5) remain unclear. The aim of this study was to investigate the association between karyotypes and gene mutations, especially in AML-M5 patients with 11q23/KMT2A (MLL) rearrangement and normal karyotype.
A total of 126 de novo AML-M5 patients were screened for mutations in the 51 genes known or suspected to have a role in myeloid malignancies or in monocytic differentiation using next-generation sequencing (NGS). Chromosome karyotype analysis was performed by R-banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT-PCR).
Of the 126 patients, one or more mutations were detected in 83.3% patients. FLT3-ITD and NRAS had the highest mutation frequency, followed by NPM1, DNMT3A, TET2, KRAS, and RUNX1. We also identified a significant difference in mutational spectrums between KMT2A-rearranged (KMT2Ar) patients and normal karyotype (NK) patients, as reflected in the average number of gene mutations per patient (1.66 vs 2.46), and in the frequencies of commonly mutated genes (FLT3-ITD: 6% vs 43.5%; NPM1: 0% vs 43.5%; RUNX1: 2.0% vs 15.2%; DNMT3A: 4% vs 26.1%; KRAS: 24.0% vs 4.35%). Patients harboring ≥3 mutations showed much lower complete remission rate than that with double mutations (P = 0.043) in high-risk group.
There was a significantly different mutation profile between KMT2Ar-patients and NK patients. Our research provided new insight into the molecular characteristics of AML-M5.
细胞遗传学和分子检测在疾病分类和预后评估方面已成为临床实践的常规手段。然而，急性单核细胞白血病（AML-M5）的分子特征仍不清楚。本研究旨在探讨核型与基因突变之间的关系，特别是在伴有 11q23/KMT2A（MLL）重排和正常核型的 AML-M5 患者中。
采用下一代测序（NGS）对 126 例初治 AML-M5 患者进行 51 个已知或疑似在髓系恶性肿瘤或单核细胞分化中起作用的基因的突变筛查。染色体核型分析采用 R 带技术，进一步通过荧光原位杂交（FISH）和/或多重逆转录聚合酶链反应（multiple RT-PCR）进行确认。
在 126 例患者中，83.3%的患者检测到一个或多个突变。FLT3-ITD 和 NRAS 的突变频率最高，其次是 NPM1、DNMT3A、TET2、KRAS 和 RUNX1。我们还发现 KMT2A 重排（KMT2Ar）患者和正常核型（NK）患者的突变谱存在显著差异，表现在每个患者的基因突变平均数（1.66 对 2.46）和常见突变基因的频率（FLT3-ITD：6%对 43.5%；NPM1：0%对 43.5%；RUNX1：2.0%对 15.2%；DNMT3A：4%对 26.1%；KRAS：24.0%对 4.35%）。在高危组中，携带≥3 个突变的患者完全缓解率明显低于携带双突变的患者（P=0.043）。
KMT2Ar 患者和 NK 患者之间存在明显不同的突变谱。我们的研究为 AML-M5 的分子特征提供了新的见解。
