TP53突变骨髓增生异常综合征患者的临床特征及染色体核型分析
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摘要
目的:探讨伴TP53突变骨髓增生异常综合征(MDS)患者的临床特征及MDS患者中TP53突变与单体核型的关系。方法:回顾性分析102例初发MDS患者TP53基因的突变情况,比较基因突变组和非突变组的临床特征,并探讨TP53突变与染色体核型尤其是单体核型的关系结果:102例MDS患者中,男性52例,女性50例,中位年龄59.5(23-83)岁,基因TP53突变的检出率为12.7%,突变多发生于MDS伴原始细胞增多亚型患者。与非突变组相比,TP53突变组血红蛋白、血小板水平偏低(P=0.001,P=0.033),而乳酸脱氢酶水平、骨髓原始细胞比例明显偏高(P=0.002,P <0.001),且中性粒细胞绝对计数、血清铁蛋白水平、β2微球蛋白水平差异均无统计学意义。TP53突变患者染色体核型异常发生率为90.9%,其中72.7%为单体核型。TP53基因突变组单体核型的发生率明显高于非突变组(P <0.001)。TP53突变合并单体核型的MDS患者出现在IPSS-R预后评分系统中预后差及预后极差组。结论:伴TP53突变的MDS患者具有独特的临床特征且单体核型发生率高,总体预后不良。
Objective: To investigate the clinical characteristics of myelodysplastic syndrome(MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients. Methods: The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed. Results: Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5(23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower(P=0.001,P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group(P=0.002, P<0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group(P<0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk. Conclusion: MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.
Objective: To investigate the clinical characteristics of myelodysplastic syndrome(MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients. Methods: The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed. Results: Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5(23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower(P=0.001,P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group(P=0.002, P<0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group(P<0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk. Conclusion: MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.
引文
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6 Tefferi A,Idossa D,Lasho TL,et al.Mutations and karyotype in myelodysplastic syndromes:TP53 clusters with monosomal karyotype,RUNX1 with trisomy 21,and SF3B1 with inv(3)(q21q26.2)and del(11q).Blood Cancer J,2017;7(12):658.
7 Arber DA,Orazi A,Hasserjian R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.Blood,2016;127(20):2391-2405.
8 Greenberg PL,Tuechler H,Schanz J,et al.Revised international prognostic scoring system for myelodysplastic syndromes.Blood,2012;120(12):2454-2465.
9 Ganguly BB,Kadam NN.Mutations of myelodysplastic syndromes(MDS):An update.Mutat Res Rev Mutat Res,2016;769:47-62.
10 Bejar R,Stevenson K,Abdel-Wahab O,et al.Clinical effect of point mutations in myelodysplastic syndromes.N Engl J Med,2011;364(26):2496-2506.
11 Breems DA,Van Putten WL,De Greef GE,et al.Monosomal karyotype in acute myeloid leukemia:a better indicator of poor prognosis than a complex karyotype.J Clin Oncol,2008;26(29):4791-4797.
12 Vaidya R,Caramazza D,Begna KH,et al.Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemiafree survival.Blood,2011;117(21):5612-5615.
13 Patnaik MM,Hanson CA,Hodnefield JM,et al.Monosomal karyotype in myelodysplastic syndromes,with or without monosomy7 or 5,is prognostically worse than an otherwise complex karyotype.Leukemia,2011;25(2):266-270.
14 Valcarcel D,Adema V,Sole F,et al.Complex,not monosomal,karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome.J Clin Oncol,2013;31(7):916-922.
15 McQuilten ZK,Sundararajan V,Andrianopoulos N,et al.Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes.Cancer,2015;121(17):2892-2899.
16 Gangat N,Mudireddy M,Lasho TL,et al.Mutations and prognosis in myelodysplastic syndromes:karyotype-adjusted analysis of targeted sequencing in 300 consecutive cases and development of a genetic risk model.Am J Hematol,2018;93(5):691-697.
17 Schanz J,Tuchler H,Sole F,et al.Monosomal karyotype in MDS:explaining the poor prognosis?Leukemia,2013;27(10):1988-1995.
18 Lindsley RC,Ebert BL.The biology and clinical impact of genetic lesions in myeloid malignancies.Blood,2013;122(23):3741-3748.
2 Kawankar N,Vundinti BR.Cytogenetic abnormalities in myelodysplastic syndrome:an overview.Hematology,2011;16(3):131-138.
3 Pellagatti A,Boultwood J.The molecular pathogenesis of the myelodysplastic syndromes.Eur J Haematol,2015;95(1):3-15.
4 Reinig E,Yang F,Traer E,et al.Targeted next-generation sequencing in myelodysplastic syndrome and chronic myelomonocytic leukemia aids diagnosis in challenging cases and identifies frequent spliceosome mutations in transformed acute myeloid leukemia.Am J Clin Pathol,2016;145(4):497-506.
5 Anelli L,Pasciolla C,Zagaria A,et al.Monosomal karyotype in myeloid neoplasias:a literature review.Onco Targets Ther,2017;10:2163-2171.
6 Tefferi A,Idossa D,Lasho TL,et al.Mutations and karyotype in myelodysplastic syndromes:TP53 clusters with monosomal karyotype,RUNX1 with trisomy 21,and SF3B1 with inv(3)(q21q26.2)and del(11q).Blood Cancer J,2017;7(12):658.
7 Arber DA,Orazi A,Hasserjian R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.Blood,2016;127(20):2391-2405.
8 Greenberg PL,Tuechler H,Schanz J,et al.Revised international prognostic scoring system for myelodysplastic syndromes.Blood,2012;120(12):2454-2465.
9 Ganguly BB,Kadam NN.Mutations of myelodysplastic syndromes(MDS):An update.Mutat Res Rev Mutat Res,2016;769:47-62.
10 Bejar R,Stevenson K,Abdel-Wahab O,et al.Clinical effect of point mutations in myelodysplastic syndromes.N Engl J Med,2011;364(26):2496-2506.
11 Breems DA,Van Putten WL,De Greef GE,et al.Monosomal karyotype in acute myeloid leukemia:a better indicator of poor prognosis than a complex karyotype.J Clin Oncol,2008;26(29):4791-4797.
12 Vaidya R,Caramazza D,Begna KH,et al.Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemiafree survival.Blood,2011;117(21):5612-5615.
13 Patnaik MM,Hanson CA,Hodnefield JM,et al.Monosomal karyotype in myelodysplastic syndromes,with or without monosomy7 or 5,is prognostically worse than an otherwise complex karyotype.Leukemia,2011;25(2):266-270.
14 Valcarcel D,Adema V,Sole F,et al.Complex,not monosomal,karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome.J Clin Oncol,2013;31(7):916-922.
15 McQuilten ZK,Sundararajan V,Andrianopoulos N,et al.Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes.Cancer,2015;121(17):2892-2899.
16 Gangat N,Mudireddy M,Lasho TL,et al.Mutations and prognosis in myelodysplastic syndromes:karyotype-adjusted analysis of targeted sequencing in 300 consecutive cases and development of a genetic risk model.Am J Hematol,2018;93(5):691-697.
17 Schanz J,Tuchler H,Sole F,et al.Monosomal karyotype in MDS:explaining the poor prognosis?Leukemia,2013;27(10):1988-1995.
18 Lindsley RC,Ebert BL.The biology and clinical impact of genetic lesions in myeloid malignancies.Blood,2013;122(23):3741-3748.