Clinical Significance Of FLT3Internal Tandem Duplication Mutation In Acute Myeloid Leukemia And An Experimental Study Of Its Targeted Therapy

Objective:To explore the clinical significance of FLT3-ITD mutation in AML, toobserve the role of FLT3targeted inhibitor sorafenib and arsenic trioxide on the celllines with FLT3-ITD mutations, provide experimental basis for clinical application.Methods:1. Analysis retrospectively on patients’ gender, age, blood, bone marrowcytology, karyotype, immunophenotype and prognosis,who was diagnosised withAML during the January2010~March2012in First Affiliated Hospital of NanchangUniversity, Department of Hematology.2. CCK-8method was used to detect the proliferation inhibition of THP-1(FLT3-WT cell line), MV4;11(FLT3-ITD cell line) under sorafenib; and thesynergistic inhibition of MV4;11under sorafenib and arsenic trioxide.3. Flow cytometry was used to detect cell apoptosis and cell cycle.4. SPSS16.0was used to performe all calculations, P <0.05were consideredstatistically significant.Results:1. In63cases of de novo AML patients,11cases were FLT3-ITD+, the mutationrate was17.5%.2. In FLT3-ITD+patients, peripheral blood leukocytes count, and the percentageof bone marrow blast cell were significantly higher than that of FLT3-ITD-patients,P<0．05.3. The DFS and OS of FLT3-ITD+patients was shorter than that of FLT3-ITD-patients, P<0．05.4. Sorafenib can inhibit the proliferation of THP-1cell lines, and the inhibition rateincreased gradually with increasing dose.5. Sorafenib and arsenic trioxide can inhibit the proliferation of MV4;11cell lines,the inhibition rate increased gradually with increasing dose, combinate the two drugscan inhibit the proliferation of MV4;11synergistically. 6. Sorafenib can increase the proportion of cells in G0/G1phase, reduce theproportion of cells in S, G2/M phase; when combined with arsenic trioxide canincrease the proportion of cells in G0/G1and S phase, cells in G2/M phase weresignificantly reduced.7. Sorafenib and arsenic trioxide can induce apoptosis of MV4;11cell lines,combinate the two drugs can induce apoptosis of FLT3-ITD cell lines synergistically.Conclusion:1. The mutation rate of FLT3-ITD in AML was17.5%; the main clinical features ofFLT3-ITD positive patients was high blast cells, shorter DFS and OS.2. Sorafenib can inhibit the proliferation of FLT3-WT cell lines, and it is dosedependent.3. Sorafenib and arsenic trioxide can effect MV4;11cell lines on proliferation andapoptosis, combinate the two drugs can effect synergistically.