急性淋巴细胞白血病患儿SLC19A1基因多态性与临床预后和甲氨蝶呤化疗毒性的相关性研究
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摘要
目的考察急性淋巴细胞白血病(ALL)患儿SLC19A1 rs1051296 G> T基因多态性对临床预后和甲氨蝶呤(MTX)化疗毒性的影响。方法收集134例ALL患儿的外周血,提取基因组DNA,采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术分析SLC19A1 rs1051296 G> T基因型。结果SLC19A1 rs1051296 TT基因型患儿的复发率(0)显著低于GG/GT基因型患儿(12. 50%),无事件生存率(94. 74%)显著高于GG/GT基因型患儿(80. 21%)。除了GG基因型患儿的血液毒性发生率(13. 79%)显著低于GT基因型患儿(38. 81%)以外,3种基因型之间的其余MTX化疗毒性发生率差异无统计学意义。结论 SLC19A1 rs1051296 G> T基因多态性与ALL患儿临床预后和MTX化疗的血液毒性显著相关。
Objective To investigate the association between SLC19 A1 rs1051296 G > T polymorphisms and clinical prognosis and toxicities of methotrexate( MTX) chemotherapy in children with acute lymphoblastic leukemia( ALL). Methods Peripheral blood samples were obtained from children with ALL( n = 134) to extract genome DNA. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry( MALDI-TOF-MS) was used to detect the genotypes of SLC19 A1 rs1051296 G > T polymorphisms. Results The relapse rate in children with SLC19 A1 rs1051296 TT genotype( 0) was significantly lower than those in GG/GT genotype carriers( 12. 50%). The event free survival( EFS) in patients with TT genotype( 94. 74%) was significantly higher than those in GG/GT genotype carriers( 80. 21%). The incidences of hematological disorders in children with GG genotype( 13. 79%) were significantly lower than those in GT genotype carriers( 38. 81%). There were no statistically significant differences in the incidences of other adverse events among three genotypes. Conclusion SLC19 A1 rs1051296 G > T polymorphisms were significantly associated with clinical prognosis of ALL children and hematological toxicities of MTX.
Objective To investigate the association between SLC19 A1 rs1051296 G > T polymorphisms and clinical prognosis and toxicities of methotrexate( MTX) chemotherapy in children with acute lymphoblastic leukemia( ALL). Methods Peripheral blood samples were obtained from children with ALL( n = 134) to extract genome DNA. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry( MALDI-TOF-MS) was used to detect the genotypes of SLC19 A1 rs1051296 G > T polymorphisms. Results The relapse rate in children with SLC19 A1 rs1051296 TT genotype( 0) was significantly lower than those in GG/GT genotype carriers( 12. 50%). The event free survival( EFS) in patients with TT genotype( 94. 74%) was significantly higher than those in GG/GT genotype carriers( 80. 21%). The incidences of hematological disorders in children with GG genotype( 13. 79%) were significantly lower than those in GT genotype carriers( 38. 81%). There were no statistically significant differences in the incidences of other adverse events among three genotypes. Conclusion SLC19 A1 rs1051296 G > T polymorphisms were significantly associated with clinical prognosis of ALL children and hematological toxicities of MTX.
引文
[1] GERVASINI G,DE MURILLO S G,JIMNEZ M,et al. Effect of polymorphisms in transporter genes on dosing,efficacy and toxicity of maintenance therapy in children with acute lymphoblastic leukemia[J/OL]. Gene,2017,628:72-77. 2017-09-10[2018-05-22]. http://linkinghub. elsevier. com/retrieve/pii/S0378-1119(17)30538-3.
[2] ZGHEIB N K,AKRA-ISMAIL M,ARIDI C,et al. Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in Lebanese children with acute lymphoblastic leukemia[J]. Pharmacogenet Genomics,2014,24(8):387-396.
[3]中华医学会儿科学分会血液学组,中华儿科杂志编辑委员会.儿童急性淋巴细胞白血病诊疗建议(第三次修订草案)[J].中华儿科杂志,2006,44(5):392-395.
[4]魏盈盈,焦溦溦,程思,等.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度与不良反应的相关性[J].中国医院药学杂志,2014,34(22):1915-1918.
[5]叶阿里,张海燕,窦亚玲,等.基质辅助激光解吸电离飞行时间质谱技术检测药物代谢酶基因多态性平台的建立[J].现代检验医学杂志,2016,31(5):30-33.
[6] WANG S M,SUN L L,WU W S,et al. MiR-595 suppresses the cellular uptake and cytotoxic effects of methotrexate by targeting SLC19A1 in CEM/C1 cells[J]. Basic Clin Pharmacol Toxicol,2018,123(1):8-13.
[7] WANG S M,SUN L L,ZENG W X,et al. Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia[J].Med Oncol,2014,31(7):62.
[2] ZGHEIB N K,AKRA-ISMAIL M,ARIDI C,et al. Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in Lebanese children with acute lymphoblastic leukemia[J]. Pharmacogenet Genomics,2014,24(8):387-396.
[3]中华医学会儿科学分会血液学组,中华儿科杂志编辑委员会.儿童急性淋巴细胞白血病诊疗建议(第三次修订草案)[J].中华儿科杂志,2006,44(5):392-395.
[4]魏盈盈,焦溦溦,程思,等.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度与不良反应的相关性[J].中国医院药学杂志,2014,34(22):1915-1918.
[5]叶阿里,张海燕,窦亚玲,等.基质辅助激光解吸电离飞行时间质谱技术检测药物代谢酶基因多态性平台的建立[J].现代检验医学杂志,2016,31(5):30-33.
[6] WANG S M,SUN L L,WU W S,et al. MiR-595 suppresses the cellular uptake and cytotoxic effects of methotrexate by targeting SLC19A1 in CEM/C1 cells[J]. Basic Clin Pharmacol Toxicol,2018,123(1):8-13.
[7] WANG S M,SUN L L,ZENG W X,et al. Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia[J].Med Oncol,2014,31(7):62.