Zhou Feng, Chao Hongying, Lu Xuzhang, Chen Tao, Yang Jianhe, Jiang Naike, Cen Ling, Zhou Min
Department of Hematology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213003, China. Email:
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Jun 10;36(6):556-560. doi: 10.3760/cma.j.issn.1003-9406.2019.06.006.
To characterize the molecular genetics of 81 patients with acute monocytic leukemia (AML).
Fluorescence in situ hybridization (FISH) was employed to detect MLL gene rearrangements. Combined mutations of 17 genes were detected by DNA-based PCR and Sanger sequencing.
Sixty seven patients were found to harbor at least one mutation. The most commonly mutated gene was NPM1 (n=18), which was followed by FLT3-ITD (n=16), NRAS (n=16), DNMT3A (n=15), TET2 (n=12), RUNX1 (n=11) and KRAS (n=9). Based on the functions of mutated genes, the most frequently involved genes were those involved in DNA methylation (38.27%), tyrosine kinase receptor signaling (32.1%), transcription regulation (28.4%), and RAS pathway (24.7%). Single gene mutation predominated in patient with cytogenetic abnormalities, while coexistence of 2 mutations have predominated in patient with normal cytogenetic findings. Stratified by cytogenetic findings, patients with single gene mutations (intermediate-risk group) had significantly higher complete remission (CR) rates than those with ≥2 gene mutations (unfavorable-risk group) (91.7% vs. 57.6% , 87.5% vs. 25.0%, P =0.0319, 0.0117, respectively).
Over 80% of AML patients were found to harbor at least one mutation. Their clinical phenotype and prognosis may be impacted by the synergy of MLL gene rearrangement and multiple mutations. For patients under the same risk stratification, the number of mutations is reversely correlated with the CR rate.
对81例急性单核细胞白血病（AML）患者的分子遗传学特征进行分析。
采用荧光原位杂交（FISH）检测MLL基因重排。通过基于DNA的聚合酶链反应（PCR）和桑格测序检测17个基因的联合突变。
67例患者至少存在一种突变。最常发生突变的基因是NPM1（n = 18），其次是FLT3-ITD（n = 16）、NRAS（n = 16）、DNMT3A（n = 15）、TET2（n = 12）、RUNX1（n = 11）和KRAS（n = 9）。根据突变基因的功能，最常涉及的基因是参与DNA甲基化的基因（38.27%）、酪氨酸激酶受体信号传导相关基因（32.1%）、转录调控相关基因（28.4%）和RAS途径相关基因（24.7%）。细胞遗传学异常的患者以单基因突变为主，而细胞遗传学结果正常的患者以2种突变共存为主。根据细胞遗传学结果分层，单基因突变患者（中危组）的完全缓解（CR）率显著高于≥2种基因突变患者（高危组）（分别为91.7%对57.6%，87.5%对25.0%，P = 0.0319，0.0117）。
超过80%的AML患者至少存在一种突变。MLL基因重排和多种突变的协同作用可能影响其临床表型和预后。对于处于相同风险分层的患者，突变数量与CR率呈负相关。
