caa a22 4500 463256247 CHVBK 20180405153356.0 cr unu---uuuuu 170326e20071001xx s 000 0 eng 10.1007/s00277-007-0325-3 doi (NATIONALLICENCE)springer-10.1007/s00277-007-0325-3 Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia [Elektronische Daten] [Natasa Colovic, Natasa Tosic, Sanja Aveic, Marija Djuric, Natasa Milic, Vladimir Bumbasirevic, Milica Colovic, Sonja Pavlovic] Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid leukemia (AML). FLT3/ITD and FLT3/D835 mutations were analyzed in 113 Serbian adult AML patients using polymerase chain reaction. Twenty patients were found to be FLT3/ITD positive (17.7%). The mutations occurred most frequently in M5 and M0 subtypes of AML. They were mainly associated with the normal karyotype. All patients harboring FLT3/ITD had a higher number of white blood cells than patients without it (p = 0.027). FLT3/ITD mutations were associated with lower complete remission (CR) rate (χ 2 = 5.706; p = 0.017) and shorter overall survival (OS; Log rank = 8.76; p = 0.0031). As for disease-free survival, the difference between FLT3/ITD-positive and FLT3/ITD-negative patients was not statistically significant (Log rank = 0.78; p = 0.3764). In multivariate analysis, the presence of FLT3/ITD mutations was the most significant prognostic factor for both OS and CR rate (p = 0.0287; relative risk = 1.73; 95% CI = 1.06-2.82). However, in the group of patients with the intermediate-risk karyotype, the mere presence of FLT3/ITD was not associated with inferior clinical outcome. FLT3/D835 point mutation was found in four patients (3.5%) only. Follow-up of the FLT3/ITD-positive patients revealed stability of this mutation during the course of the disease. However, changes in the pattern of FLT3/D835 mutations in initial and relapsed AML were observed. Our results indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy. Because FLT3/ITD mutation is a target for specific therapeutic inhibition, its early detection could be helpful in clinical practice. Springer-Verlag, 2007 AML nationallicence FLT3 mutations nationallicence Prognostic significance nationallicence Paired initial and relapsed samples nationallicence Colovic Natasa Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia aut Tosic Natasa Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut Aveic Sanja Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut Djuric Marija Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut Milic Natasa Medical Faculty, Institute of Statistics, Belgrade, Serbia aut Bumbasirevic Vladimir Medical Faculty, Institute of Histology, Belgrade, Serbia aut Colovic Milica Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia aut Pavlovic Sonja Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut Annals of Hematology Springer-Verlag 86/10(2007-10-01), 741-747 0939-5555 86:10<741 2007 86 277 https://doi.org/10.1007/s00277-007-0325-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00277-007-0325-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Colovic Natasa Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia aut NATIONALLICENCE 700 1- Tosic Natasa Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut NATIONALLICENCE 700 1- Aveic Sanja Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut NATIONALLICENCE 700 1- Djuric Marija Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut NATIONALLICENCE 700 1- Milic Natasa Medical Faculty, Institute of Statistics, Belgrade, Serbia aut NATIONALLICENCE 700 1- Bumbasirevic Vladimir Medical Faculty, Institute of Histology, Belgrade, Serbia aut NATIONALLICENCE 700 1- Colovic Milica Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia aut NATIONALLICENCE 700 1- Pavlovic Sonja Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, 11010, Belgrade, Serbia aut NATIONALLICENCE 773 0- Annals of Hematology Springer-Verlag 86/10(2007-10-01), 741-747 0939-5555 86:10<741 2007 86 277 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer