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Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia.
Ann Hematol. 2007 Oct; 86(10):741-7.AH

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.

Authors+Show Affiliations

Institute of Hematology, Clinical Center of Serbia, Belgrade, Serbia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17579862

Citation

Colovic, Natasa, et al. "Importance of Early Detection and Follow-up of FLT3 Mutations in Patients With Acute Myeloid Leukemia." Annals of Hematology, vol. 86, no. 10, 2007, pp. 741-7.
Colovic N, Tosic N, Aveic S, et al. Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. Ann Hematol. 2007;86(10):741-7.
Colovic, N., Tosic, N., Aveic, S., Djuric, M., Milic, N., Bumbasirevic, V., Colovic, M., & Pavlovic, S. (2007). Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. Annals of Hematology, 86(10), 741-7.
Colovic N, et al. Importance of Early Detection and Follow-up of FLT3 Mutations in Patients With Acute Myeloid Leukemia. Ann Hematol. 2007;86(10):741-7. PubMed PMID: 17579862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia. AU - Colovic,Natasa, AU - Tosic,Natasa, AU - Aveic,Sanja, AU - Djuric,Marija, AU - Milic,Natasa, AU - Bumbasirevic,Vladimir, AU - Colovic,Milica, AU - Pavlovic,Sonja, Y1 - 2007/06/20/ PY - 2007/03/12/received PY - 2007/05/28/accepted PY - 2007/6/21/pubmed PY - 2008/1/30/medline PY - 2007/6/21/entrez SP - 741 EP - 7 JF - Annals of hematology JO - Ann Hematol VL - 86 IS - 10 N2 - 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. SN - 1432-0584 UR - https://www.unboundmedicine.com/medline/citation/17579862/Importance_of_early_detection_and_follow_up_of_FLT3_mutations_in_patients_with_acute_myeloid_leukemia_ L2 - https://dx.doi.org/10.1007/s00277-007-0325-3 DB - PRIME DP - Unbound Medicine ER -