急性髓性白血病N-ras基因突变的检测及临床意义

目的 研究急性髓性白血病（AML）患者中N-ras基因突变的检出率及其临床意义.方法 采用聚合酶链式反应（PCR）及序列分析方法检测117例初治AML患者N-ras基因第12、13和61位密码子的突变情况.结果 在117例AML患者中,发现N-ras基因突变9例,包括50例FAB分型M2中1例,35例M4中5例,16例M5中2例及6例M6中1例,而在2例M0、2例M1及6例M3中未发现N-ras基因突变,总检出率为7.7%.共检出3例第12密码子GGT→GAT突变,1例第13密码子GGT→GAT突变和5例第61密码子突变（包括3例CAA→CGA突变,1例CAA→AGA突变,1例CAA→AAA突变）.N-ras突变在正常核型中的检出率（4/30,13.3%）高于在异常核型中的检出率（1/19,5.3%）,但差异无统计学意义（P〉0.05）.结论 在AML患者中可以检测到N-ras基因突变,该突变可发生在N-ras基因的第61、12和13密码子,可能在AML发病机制中发挥一定作用.

Detection and significance of N-ras mutations in acute myeloid leukemia

Objective To investigate the detection rate of N-ras mutations in adult acute myeloid leukemia and its clinic significance.Methods We detected typical N-ras mutations at codon 12,codon 13 and codon 61 of N-ras gene in 117 untreated AML patients using polymerase chain reaction （PCR） followed by sequence analysis.Results Nine cases with N-ras mutation were found in 117 AML patients,including one in 50 cases of the French-American-British （FAB） subtype M2,five in 35 cases of M4,two in 16 cases of M5 and one in 6 cases of M6.No mutation was found in 2 with M0,2 with M1 and 6 with M3.The total detection rate of N-ras mutations was 7.7% in 117 AML patients.In 9 patients with N-ras mutations,3 were in codon 12 with the GGT to GAT conversion,1 was in codon 13 with the GGT to GAT conversion and 5 were in codon 61（ including 3 CAA to CGA conversion,1 CAA to AGA conversion and 1 CAA to AAA conversion）.The detection rate of N-ras mutations in normal karyotype（4 of 30,13.3%） was higher than that in abnormal karyotype （1 of 19,5.3%）,but no statistical significance difference was observed （P0.05）.Conclusions The mutations at codon 61,12 and 13 of N-ras gene may be involved in the pathogenesy of acute myeloid leukemia.