融合基因ETV6-NTRK3在恶性血液病中的表达及临床意义

Fusion gene of ETV6-NTRK3 presence in hematological system malignant tumor and its clinical significance

目的:研究融合基因ETV6-NTRK3在血液系统恶性肿瘤中的表达水平及其特点,并寻找其与免疫表型之间的关系,初步探讨该融合基因在临床诊断、治疗及预后判断等方面的价值。方法:收集未治疗的血液系统恶性肿瘤患者的骨髓液共47例及其中14例经标准化疗方案化疗2个疗程的急性髓细胞白血病(AML-M2)患者的骨髓液,釆用逆转录聚合酶链反应(RT-PCR)方法扩增特定的融合基因片段。同时,对47例初治患者使用流式细胞术进行FCM免疫表型分析。结果:47例血液系统恶性肿瘤中,有2例表达ETV6-NTRK3融合基因,均为AML-M2a患者,其在M2中阳性率约为14%(2/14)。未能查到NTRK3-ETV6和NTRK3基因。结论:①约有14%AML-M2患者存在ETV6-NTRK3融合基因t(12;15)(p12;q25)。均为M2a,为老龄患者,且伴有骨髓纤维化;②目前的标准化疗方案,对表达ETV6-NTRK3融合基因患者效果不佳,为难治性白血病,患者预后不良;③FCM免疫表型分析结果表明,表达ETV6-NTRK3融合基因的为AML M2型,表达CD13和CD33,且CD13表达强于CD33,不表达CD14,白血病细胞起源早,分化程度差,恶性度高。

Objective：To investigate the expression of the fusion gene of ETV6-NTRK3 and its feature in hematological malignagcy; explore the relationship between the fusion gene and its immunophenotype; evaluate its value in the clinical dignosis, therapy and prognosis . Method： Collect 47 samples which were untreated and 14 samples of AML-M2 which were therapied by two courses with standard chemotherapy regimen, to amplify specific fusion gene fragment by RT-PCR method, flow cytometry was applied to analyze the immunophenotype of the 47 samples. Result：Under the ultraviolet light, two samples expressed ETV6-NTRK3 fusion gene among 47 sampies. The positive rate was 14% in AML-M2 （2/14）. We could not detect any reciprocal products of NTRK3- ETV6. A nomal NTRK3 message was also undetectable. Conclusion ： （1） About 14% AML-M2 can express ETV6- NTRK3 fusion gene t（12;15） （p13;q25）. All of them are AML-M2a. （2）The present standard therapic program can not take any effect on the patients with ETV6-NTRK3 fusion genes which is refractory leukemia, so the prognosis is badly. （3）According to the FCM immunophenotype analysis, the patients with ETV6-NTRK3 fusion gene expressed CD13 and CD33, and the expression of CD13 is stronger than that of CD33. No-CD14 expression. It signified the leukemic cell of the patients originated early, differentiated badly, and was high-grade malignancy.