儿童白血病患者PTPN11基因突变及其临床意义分析

Analysis of PTPN11 Mutation in Children Leukemia and Its Clinical Significance

本研究探讨儿童白血病患者PTPN11基因的突变率及其临床意义。提取初诊101例急性淋巴细胞白血病(ALL)、26例急性髓系白血病(AML)、3例慢性髓系白血病(CML)、1例幼年粒单核细胞白血病(JMML)患者外周血基因组DNA,运用聚合酶链反应(PCR)扩增PTPN11基因突变热点外显子3、8及13,并对研究病例进行临床随访,分析PTPN11基因突变的临床意义。结果表明:在101例ALL中发生PTPN11突变10例,突变率9.9%。PTPN11基因突变与初诊时年龄、性别、白细胞数、强的松敏感试验反应、临床危险度、疾病复发等因素无关(P>0.05)。在26例AML中发生突变2例,其中AML-M2及M4各1例;在3例CML中无1例突变;在1例JMML中可见PTPN11基因突变。结论:PTPN11基因3号外显子E76密码子是儿童白血病的突变热点,G503E为新检测出的JMML突变方式,PTPN11基因突变与初诊时年龄、性别、白细胞数、强的松敏感试验反应、临床危险度、早期复发等无关。

This study was aimed to explore the frequency of PTPNll mutation in children with leukemia and its clinical significance. Genomic DNAs were extracted from peripheral leukocytes of 131 patients with leukemia, including 101 cases of ALL, 26 cases of AML, 3 cases of CML and 1 case of juvenil myelomonocytic leukemia （JMML）. The sequences of PTPN11 exons 3, 8, 13 were amplified by polymerase chain reaction （PCR）, and the clinical characteristics of positive patients were analyzed. The results indicated that the PTPN11 mutation was found in 10 cases （9.9%） from newly diagnosed 101 cases of ALL. Grouping the newly diagnosed ALL children by various clinical features, it was found that the PTPN11 mutation did not show associations with sex, age, white blood cell （WBC） count, prednisone test sensitivity, clinical risk and disease recurrences at the first visit （P 〉 0.05 ）. PTPNll mutations were found in 2 cases out of 26 AML patients, including one AML-M2 and one AML-M4. No PTPNll mutation in 3 CML patients was found. Exon 13 mutation of PTPN11 gene was found in 1 case of JMML. It is concluded that the E76 of exon 3 is the hot spot of PTPNII mutation in children leukemia. The novel G503E（ 1508G 〉 A） mutation is detected in one JMML patient. The PTPN11 mutation does not associate with the sex, age, WBC count, prednisone sensitive test and early recurrence.