Fusion Gene Of ETV6-NTRK3 Presence In Hematological System Tumor And Its Clinic Significance

Objective To investigate fusion gene of ETV6-NTRK3 expression and its feature in hematological system malignant tumor ;to search the relationship between it and the immunophenotype; to approach it causion tumorigenic molecular biology mechamism , application clinical dignosis and therapy.Methods collect untreated patients of hematological system malignant tumor bone marrow 47 samples and 14 samples of AML-M2 which was therapied two course with standard chemotherapy regimen (EDTA anticoagulation).The patients were from JiNan central hospital,Shan Dong University Qi Lu hospital and Shan Dong province hospital from 2004.8 to 2004.12. application Trizol to extract RNA, to design specific PCR primer ,to amplify spefic fusion gene fragment by RT-PCR method.analysising the RT-PCR production on 3% agarose gel electrophoresis.Meanwhile,applying flow cytometry to analysis the immunophenotype of the 47 samples.Results(1)under the ultraviolet light,among 47 patints of hematological system malignant tumor,there are two patients of AML-M₂ expression ETV6-NTRK3 fusion gene,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.(2)The two patients were applied to 2-3 standard dose DA or MA therapicprogram .the result were NR. Rechecking the ETV6-NTRK3 fusion gene was still existence.lt hints that chemical treatment is not on effect with the patients of ETV6-NTRK3 fusion gene,and it is refractory leukemia.because of the physical state or economy etc, two patients failed to continue treatment with HD-Arac.but two patients live time exceeded six months.(3)meso-age was 65 years old.we found two patients existed myelofibrosis through bone marrow biopsy.(4)FCM immunophenotype analysis:the male,52 years old (data was from Tian Jin hematological institute) CDn770% , CD3396% , HLA-DR95% , CD,378% , CD3494%, CD2257%.the female,78 years old, CD,384.3%, CD3481.5%, CD3334.3%, CDn775.2%, HLA-DR73.6%.Conclusions(l)about 14% AML-M2 can express ETV6-NTRK3 fusion gene t(12;15) (pl3;q25).they are M2a.all are elder patients,and have myelofibrosis.(2)The present standard therapic program can not take effect on the patients of ETV6-NTRK3 fusion gene,and it is refractory leukemia.(3)According to the FCM immunophenotype analysis, the patients of ETV6-NTRK3 fusion gene is AML-M2,expression CD13 and CD33,and CD13 is stronger than CD33.non-expression CD14.the leukemic cell of the patients genesis early,diffrentiate badly,is hypsi-malignancy.(4)ETV6-NTRK3 fusion gene possess oncogene activity, maybe that HLH domain on ETV6 mediate heterodimers or homodimers autophorylation,and activate PTK on NTRK3 via ligand-independent, precipiate hematopoietic cell maliganant transformation, via the Ras-Rafl-Mekl-Erkl/2 mitogenic pathway and the PI3K pathway.