MDS、MDS/AML及AML基因突变的频谱分析

doi:10.3969/j.issn.1000-8535.2018.04.001

广州医药 ›› 2018, Vol. 49 ›› Issue (4): 1-6.DOI: 10.3969/j.issn.1000-8535.2018.04.001

• 论著 • 下一篇

MDS、MDS/AML及AML基因突变的频谱分析

胡偏¹, 毛敏², 王燕³, 潘歆³, 农卫霞³, 龙珍珠玛³, 章大谦³, 张红霞³, 吴广胜³

1 新疆石河子大学医学院 (石河子 832000);
2 新疆维吾尔自治区人民医院血液科(乌鲁木齐 830001);
3 新疆石河子大学医学院第一附属医院血液科(石河子 832000)

收稿日期:2018-03-08 出版日期:2018-07-20 发布日期:2021-11-29
通讯作者: 吴广胜,E-mail:hemotology@126.com
基金资助:
石河子大学医学院第一附属医院院级课题(PJ2016004)

The analysis of spectrum of gene mutations in MDS、MDS/AML and AML

HU Pian¹, MAO Min², WANG Yan³, PAN Xin³, NONG Weixia³, LONG Zhenzhuma³, ZHANG Daqian³, ZHANG Hongxia³, WU Guangsheng³

1 The Medical College of Shihezi University, Xinjiang, Shihezi 832000, China;
2 Department of Hematology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 832001,China;
3 Department of Hematology, The First Affiliated Hospital of the Medical College Shihezi University, Shihezi 830000, China

Received:2018-03-08 Online:2018-07-20 Published:2021-11-29

摘要/Abstract

摘要： 目的探讨MDS、MDS/AML及原发AML基因突变频谱的异同点及其临床意义。方法选取98例MDS患者、32例MDS/AML患者及234例原发AML患者为研究对象,利用二代测序技术检测基因突变。结果 MDS组中突变率较高的基因突变为TET2(16.7%,16/96)、U2AF1(12.0%,6/50)、SF3B1(11.8%,9/76);MDS/AML组中突变率较高的基因突变为TP53(33.3%,2/6)、DNMT3A(30%,6/20)、IDH2(21.1%,4/19);原发AML组中突变率较高的基因突变为FLT3-ITD(18.0%,42/233)、NPM1(16.3%,38/233)、DNMT3A(14.9%,14/94)。DNMT3A(P=0.006)、IDH2(P=0.004)及NPM1(P=0.002)等基因突变在MDS与MDS/AML两组间的突变率有统计学差异;FLT3-ITD(P=0.001)、NPM1(P=0.002)、CEBPA(P=0.011)及IDH2(P=0.019)等基因突变在MDS与原发AML两组间的突变率有统计学差异;所有受检基因突变在MDS/AML与原发AML两组间的基因突变的突变率无统计学差异(P＞0.05)。结论 MDS、MDS/AML及原发AML基因突变的突变频谱具有相似性及异质性,从MDS到MDS/AML、原发AML基因突变的变化不仅影响疾病转归及预后而且可帮助鉴别MDS/AML和原发AML。

关键词: 骨髓增生异常综合征, 急性髓系白血病, 基因突变, 二代测序

Abstract: Objective To explore the similarities and differences of spectrum of gene mutations in patients with myelodysplastic syndrome, MDS/AML and de novo acute myeloid leukemia and their clinical significance. Methods 98 patients with MDS, 32 patients with MDS/AML, 234 patients with de novo AML were selected. Gene mutations were detected by second generation sequencing. Results The most frequent mutations in MDS were as follows:TET2(16.7%, 16/96), U2AF1(12.0%, 6/50), SF3B1(11.8%, 9/76); The most frequent mutations in MDS/AML were TP53(33.3%, 2/6), DNMT3A(30%, 6/20), IDH2 (21.1%, 4/19);The most frequent mutations in de novo AML were FLT3-ITD(18.0%, 42/233), NPM1(16.3%, 38/233), DNMT3A(14.9%, 14/94); DNMT3A(P=0.006),IDH2(P=0.004) and NPM1(P=0.002) were statistical difference between MDS and MDS/AML; FLT3-ITD(P=0.001),NPM1(P=0.002),CEBPA(P=0.011) and IDH2(P=0.019) were statistical difference between MDS and de novo AML;There were no siatistical significance (P>0.05) in the frequency of all detected gene mutations between MDS/AML and AML. Conclusion The spectrum of gene mutation of MDS, MDS/AML and primary AML have similarities and heterogeneity.The changes of gene mutations from MDS to MDS/AML and de novo AML not only affect disease outcome and prognosis, but also help to identify MDS/AML and de novo AML.

Key words: Myelodysplastic syndrome, De novo acute myeloid leukemia, Gene mutation, Next-generation sequencing

胡偏, 毛敏, 王燕, 潘歆, 农卫霞, 龙珍珠玛, 章大谦, 张红霞, 吴广胜. MDS、MDS/AML及AML基因突变的频谱分析[J]. 广州医药, 2018, 49(4): 1-6.

HU Pian, MAO Min, WANG Yan, PAN Xin, NONG Weixia, LONG Zhenzhuma, ZHANG Daqian, ZHANG Hongxia, WU Guangsheng. The analysis of spectrum of gene mutations in MDS、MDS/AML and AML[J]. Guangzhou Medical Journal, 2018, 49(4): 1-6.

参考文献

[1] BEJAR R, LEVINE R, EBERT B L. Unraveling the molecular pathophysiology of myelodysplastic syndromes[J]. J Clin Oncol, 2011, 29(5): 504-515.
[2] WALTER M J, SHEN D, DING L, et al. Clonal architecture of secondary acute myeloid leukemia[J].N Engl J Med, 2012, 366(12): 1090-1098.
[3] PAPAEMMANUIL E, GERSTUNG M, MALCOVATI L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes[J]. Blood, 2013, 122(22): 3616-3627.
[4] HAFERLACH T, NAGATA Y, GROSSMANN V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes[J]. Leukemia, 2014, 28(2): 241-247.
[5] XU Y, LI Y, XU Q, et al. Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing[J]. Oncotarget, 2017, 8(47): 82475-82490.
[6] XU L, GU Z H, LI Y, et al. Genomic landscape of CD34(+) hematopoietic cells in myelodysplasticsyndrome and gene mutation profiles as prognostic markers[J]. Proc Natl Acad Sci U S A, 2014, 111(23): 8589-8594.
[7] XU F, WU L Y, HE Q, et al. Exploration of the role of gene mutations in myelodysplasticsyndromes through a sequencing design involving a small number of target genes[J]. Sci Rep, 2017(7): 43113-43123.
[8] LINDSLEY R C, MAR B G, MAZZOLA E, et al. Acute myeloid leukemia ontogeny is defined bydistinct somatic mutations[J]. Blood, 2015, 125(9): 1367-1376.
[9] CARGO C A, ROWBOTHAM N, EVANS P A, et al. Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression[J]. Blood, 2015, 126(21): 2362-2365.
[10] TCGA NETWORK.Genomic and Epigenomic Landscapes of adult de novo acute myeloid leukemia[J]. N Engl J Med, 2013, 368(22): 2059-2074.
[11] SHEN Y, ZHU Y M, FAN X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia[J]. Blood, 2011, 118(20): 5593-5603.
[12] LIN P H, LI H Y, FAN S C, et al. A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice[J]. Cancer Med, 2017, 6(2): 349-360.
[13] ZHU Y M, WANG P P, HUANG J Y, et al. Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance[J]. J Transl Med, 2017, 15(1): 178-189.
[14] ANDREIA de A, MEGGENDORFER M, WOLFGANG K, et al. Cytogenetic and molecular genetic shifts in 27 genes investigated by ngs depict specific routes from mds to s-aml in 38 patients with paired samples[J]. Blood Cancer J, 2014, 124(21): 2378-2380.
[15] SHI H L, HUANG C, WANG P, et al. Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloidleukemia[J]. Leukemia, 2004, 18(3): 466-475.
[16] BACHER U, HAFERLACH C, ALPERMANN T, et al. Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms[J]. Leukemia, 2011, 25(4): 615-621.
[17] JASEK M, GONDEK L P, BEJANYAN N, et al. TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p[J]. Leukemia, 2010, 24(1): 216-219.
[18] SHIH A, ABDEL-WAHAB O, PATEL J, et al. The role of mutations in epigenetic regulators in myeloid malignancies[J]. Nat Rev Cancer, 2012, 12(9): 599-612.
[19] WALTER M, SHEN D, SHAO J, et al. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes[J]. Leukemia, 2013, 27(6): 1275-1282.
[20] EISFELD A, MRÓZEK K, KOHLSCHMIDT J, et al. The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia[J]. Leukemia, 2017, 31(10): 2211-2218.
[21] SPERLING A S, GIBSON C J, EBERT B L. The genetics of myelodysplastic syndrome: from clonal hematopoiesis to secondary leukemia[J]. Nat Rev Cancer, 2017, 17(1): 5-19.

MDS、MDS/AML及AML基因突变的频谱分析

The analysis of spectrum of gene mutations in MDS、MDS/AML and AML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价

[1]	王小拍, 杜洪, 李秀博, 刘寿生. 结肠原发性腺鳞癌和鳞癌的临床病理分析[J]. 广州医药, 2018, 49(5): 94-97.
[2]	李秀博, 杜洪, 王小拍, 李雯, 沈春辉. 537例结肠腺癌患者KRAS基因检测结果分析[J]. 广州医药, 2018, 49(4): 7-9.