Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia
Samo za registrovane korisnike
2007
Autori
Čolović, NatašaTošić, Nataša
Aveić, Sanja
Đurić, Marija
Milić, Nataša
Bumbasirević, Vladimir
Colović, Milica
Pavlović, Sonja
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 (chi(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 analy...sis, 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.
Ključne reči:
prognostic significance / paired initial and relapsed samples / FLT3 mutations / AMLIzvor:
Annals of Hematology, 2007, 86, 10, 741-747Izdavač:
- Springer, New York
DOI: 10.1007/s00277-007-0325-3
ISSN: 0939-5555
PubMed: 17579862
WoS: 000248975000007
Scopus: 2-s2.0-34548306949
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Čolović, Nataša AU - Tošić, Nataša AU - Aveić, Sanja AU - Đurić, Marija AU - Milić, Nataša AU - Bumbasirević, Vladimir AU - Colović, Milica AU - Pavlović, Sonja PY - 2007 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/273 AB - 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 (chi(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. PB - Springer, New York T2 - Annals of Hematology T1 - Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia EP - 747 IS - 10 SP - 741 VL - 86 DO - 10.1007/s00277-007-0325-3 ER -
@article{ author = "Čolović, Nataša and Tošić, Nataša and Aveić, Sanja and Đurić, Marija and Milić, Nataša and Bumbasirević, Vladimir and Colović, Milica and Pavlović, Sonja", year = "2007", abstract = "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 (chi(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.", publisher = "Springer, New York", journal = "Annals of Hematology", title = "Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia", pages = "747-741", number = "10", volume = "86", doi = "10.1007/s00277-007-0325-3" }
Čolović, N., Tošić, N., Aveić, S., Đurić, M., Milić, N., Bumbasirević, V., Colović, M.,& Pavlović, S.. (2007). Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. in Annals of Hematology Springer, New York., 86(10), 741-747. https://doi.org/10.1007/s00277-007-0325-3
Čolović N, Tošić N, Aveić S, Đurić M, Milić N, Bumbasirević V, Colović M, Pavlović S. Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. in Annals of Hematology. 2007;86(10):741-747. doi:10.1007/s00277-007-0325-3 .
Čolović, Nataša, Tošić, Nataša, Aveić, Sanja, Đurić, Marija, Milić, Nataša, Bumbasirević, Vladimir, Colović, Milica, Pavlović, Sonja, "Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia" in Annals of Hematology, 86, no. 10 (2007):741-747, https://doi.org/10.1007/s00277-007-0325-3 . .