FLT3 Mutation in Patients with Acute Promyelocytic Leukemia Has No Effect on Therapy Response.

Fms-Like tyrosine kinase 3 (FLT3) mutations are one of the most frequent genetic changes in acute myeloid leukemia (AML) and are related to poor prognosis. However, in acute promyelocytic leukemia (APL) the prognostic significance of this mutation is not firmly established. We investigated FLT3 internal tandem duplications (FLT3/ITD) or point mutation of the activation loop domain (FLT3/ALM) in initial marrow samples in 160 APL patients, also studied the impact of FLT3 mutations on disease characteristics and clinical outcome. Some of FLT3/ITD⁺ samples were further examined to determine the ITD allelic ratio(ITD-AR) using Genescan analysis. FLT3/ITD and FLT3/ALM were detected in 31 (19.4%) and 17(10.6%) of the patients, 2(1.25%) showed both ITD and ALM mutations. 19 of 31 FLT3-ITD⁺ patients were examined to determine ITD-AR, which varied from 0.11 to 1.79, with a median of 0.92. ITD-AR in 8 patients were greater than 1.0. Both mutations were associated with higher white blood cell(WBC) count at presentation(P<0.05); Among patients with WBC counts greater than 10×10⁹/L, FLT3/ITD and FLT3/ALM rates were 49.1%(26/53) and 22.6% (12/53) respectively, were both higher than those of patients with WBC counts lower than 10×10⁹/L (P<0.01). For clinical outcome, the complete remission(CR) of FLT3-ITD⁺ patients was lower than that of FLT3-ITD⁻ patients(64.5% vs 91.5%, P<0.01), however the CR rates were not significantly different between patients with and without FLT3-LAM(84.6% vs 100%, P>0.05). Six originally FLT3-ITD⁺ patients were not detectable mutation after remission; so were six patients with originally FLT3-LAM⁺; however FLT3-LAM in one originally FLT3-LAM⁺ patient reappeared after relapse. In conclusion, FLT3 mutations (FLT3/ITD or FLT3/ALM) were frequently identified in patients with newly diagnosed APL, and both mutations were associated with higher WBC count at presentation. FLT3/ITD is more frequent than ALM mutation, and predicts a poorer prognosis because of the lower CR rates, while, FLT3/ALM mutation did not show the same unfavorable prognostic effect. In our study, ITD-AR were not found significantly difference between CR and no remission patients (P>0.05)