RUNX1突变急性髓系白血病的分子学特点分析

李青芸; 崔苗; 卢绪章; 周峰; 姜乃可

doi:10.13201/j.issn.1004-2806.2022.07.013

RUNX1突变急性髓系白血病的分子学特点分析

- 南京医科大学附属常州市第二人民医院血液科(江苏常州，213003)

详细信息

通讯作者: 卢绪章，E-mail：luxuzhang2008@163.com

中图分类号: R733.71

收稿日期: 2021-12-04

刊出日期: 2022-07-01

Molecular characterization of RUNX1 gene mutation in acute myeloid leukemia

- Department of Hematology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, 213003, China

More Information

Corresponding author: LU Xuzhang, E-mail: luxuzhang2008@163.com

Received Date: 04 December 2021

Publish Date: 01 July 2022

摘要

摘要: 目的探讨RUNX1突变急性髓系白血病(AML)的分子学特点及其与部分临床参数的相关性。方法采用高通量DNA测序技术联合PCR及Sanger测序法检测30例RUNX1突变AML患者与211例RUNX1野生型AML患者的50余种髓系肿瘤基因突变。结果 ① 与RUNX1野生型患者比较，RUNX1突变AML患者中M0亚型的比例更高(10.0% vs 0.9%，P< 0.05)，细胞遗传学分组中预后良好组的比例更低(0 vs 15.9%，P< 0.05)。②RUNX1突变AML患者具有更高的SRSF2(6.7% vs 0，P< 0.05)突变发生率，更低的NPM1(3.3% vs 28.9%，P< 0.01)及CEBPA突变发生率(3.3% vs 21.3%，P< 0.05)。③30例RUNX1突变AML患者中90.0%伴有额外基因突变，与RUNX1野生型患者比较，RUNX1突变AML患者中具有2种基因突变的比例更低，≥3种以上基因突变的比例更高(P< 0.05)。④30例RUNX1突变AML患者中，与DNMT3A野生型患者比较，伴有DNMT3A突变的患者年龄更大，共存基因突变个数更多(P< 0.05)。⑤初次诱导化疗后，RUNX1突变及野生型AML患者的缓解率分别为53.3%及75.0%，差异有统计学意义(P< 0.05)。结论 RUNX1突变AML患者具有独特的分子生物学特征，并与部分临床参数相关，完全缓解率明显降低。与RUNX1野生型患者比较，RUNX1突变AML患者在基因突变个数及突变谱系上有一定的差异。
- 急性髓系白血病 /
- RUNX1基因 /
- 基因突变 /
- 基因谱
Abstract: Objective To investigate the molecular characteristics of RUNX1 gene mutation in acute myeloid leukemia(AML) and its correlation with some clinical parameters.Methods High-throughput DNA sequencing combined with Genomic DNA-PCR and Sanger sequencing were used to detect 50 target gene mutations in 30 AML patients with RUNX1 gene mutation and 211 AML patients without RUNX1 gene mutation.Results ① Compared with RUNX1 wild type, the proportion of M0 subtype in AML patients with RUNX1 mutation was significantly higher(10.0% vs 0.9%,P< 0.05), and the proportion of good prognosis group was significantly lower(0 vs 15.9%,P< 0.05). ②AML patients with RUNX1 mutation had a higher incidence of SRSF2(6.7% vs 0,P< 0.05), lower incidence of NPM1(3.3% vs 28.9%,P< 0.01) and CEBPA mutation(3.3% vs 21.3%,P< 0.05). ③Among 30 AML patients with RUNX1 mutation, 90.0% were accompanied by additional gene mutations. Compared with RUNX1 wild type, the proportion of 2 gene mutations was lower, and the proportion of 3 or more gene mutations was higher(P< 0.05). ④Compared with DNMT3A wild type, patients with DNMT3A mutation were older and had more coexisting gene mutations(P< 0.05). ⑤After the first induction chemotherapy, the remission rates of AML patients with RUNX1 mutation and without RUNX1 mutation were 53.3% and 75.0%, respectively(P< 0.05).Conclusion AML patients with RUNX1 mutation have unique molecular biological features and associated with some clinical parameters. Compared with wild type, AML patients with RUNX1 mutation have certain differences in the number of gene mutations and gene expression profile.
- acute myeloid leukemia /
- RUNX1 gene /
- gene mutation /
- gene expression profile

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表 1 RUNX1突变型与野生型AML患者的临床特征比较

临床特征	总数(241例)	RUNX1突变型(30例)	RUNX1野生型(211例)	P
性别/例(%)				0.826
男	124(51.5)	16(53.3)	108(51.2)
女	117(48.5)	14(46.7)	103(48.8)
年龄/岁	44.5(30~54)	45.5(28~52)	44(30~54)	0.678
白细胞计数/(×10⁹· L^-1)	15.8(5.6~54.9)	13.2(5.2~54.2)	18.8(5.6~55.8)	0.397
血红蛋白/(g·L^-1)	86.0(69.8~104.0)	88.0(70.5~106.0)	85.5(69.0~104.0)	0.763
血小板计数/(×10⁹· L^-1)	50.0(27.0~77.3)	53.0(35.5~73.5)	49.0(26.5~78.5)	0.360
细胞遗传学/例(%)
预后良好	31(12.9)	0	31(14.7)	0.018
预后中等	156(64.7)	22(73.3)	134(63.5)	0.435
预后不良	37(15.4)	7(23.3)	30(14.2)	0.357
资料缺失	17(7.1)	1(3.3)	16(7.6)
+8/例(%)	16(6.6)	5(16.7)	11(5.2)	0.061
FAB/例(%)
M0	5(2.1)	3(10.0)	2(0.9)	0.015
M1	11(4.6)	2(6.7)	9(4.3)	0.903
M2	56(23.2)	5(16.7)	51(24.2)	0.363
M4	29(12.0)	1(3.3)	28(13.3)	0.206
M5	129(53.5)	19(63.3)	110(52.1)	0.250
未能分型	11(4.6)	0	11(5.2)

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表 2 RUNX1突变伴FLT3-ITD及DNMT3A突变患者的临床特征比较

临床特征	FLT3-ITD		P	DNMT3A		P
临床特征	突变型(6例)	野生型(24例)	P	突变型(7例)	野生型(23例)	P
年龄/岁	46.5(32~52)	28.5(23~50)	0.177	53(46~63)	37(27~48)	0.014
白细胞计数/(×10⁹·L^-1)	22.0(5.0~77.7)	12.7(4.8~44.5)	0.455	7.0(2.1~40.5)	13.2(6.0~58.5)	0.408
血红蛋白/(g·L^-1)	91.5(72.3~116.8)	88.0(70.5~106.0)	0.846	82.5(68.0~116.8)	89.3(71.5~104.0)	1.000
血小板计数/(×10⁹·L^-1)	53.0(48.5~150.5)	53.5(26.3~72.0)	0.434	68.5(45.3~105.8)	53.0(30.0~73.0)	0.265
基因突变个数/种	3(3~5)	3(2~4)	0.521	4(4~6)	3(2~3)	0.001
完全缓解/例(%)	4(66.7)	15(62.5)	1.000	2(28.6)	14(60.9)	0.204

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