Prognostic Significance of FLT3 Internal Tandem Duplication in Acute Myeloid Leukemia with Normal Karyotype

ABSTRACT

BACKGROUND: Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplication (ITD) in the juxtamembrane region are found in 20~30% of the adults with acute myeloid leukemia (AML). The allelic ratio of FLT3/ITD (ITD-AR), as assessed by Genescan analysis, has been reported to carry prognostic significance in AML patients who have normal karyotype. METHODS: FLT3/ITD was studied by PCR in 113 adults with AML including 55 patients with normal karyotype. Genescan analysis was performed for the PCR products to determine the allelic distribution. The results were correlated with the prognostic factors. RESULTS: FLT3/ITD was found in 23% of the total AML patients and in 32.7% of those patients with normal karyotype. The mutation was related to a high WBC count, a high serum LD level and a low percentage of CD34 positive cells. The ITD-AR ranged from 0.05 to 8.27 (median, 0.61). The patients with a high ITD-AR (> or =0.7) had significantly higher WBC count and LD level than those without FLT3/ITD. On multivariate analysis, a high ITD-AR as well as FLT3/ITD were confirmed to be independent adverse prognostic factors for AML patients with normal karyotype. CONCLUSION: This study demonstrated that a high ITD-AR and FLT3/ITD had major adverse impacts on the prognostic relevance for AML patients with normal karyotype.