Inferior prognostic outcome in acute promyelocytic leukemia with alterations of FLT3 gene

Abstract

Alterations of the FLT3 gene, in the form of internal tandem duplications (ITD) and D835 point mutations, occur frequently in acute promyelocytic leukemia (APL). We therefore evaluated the frequency and clinical relevance of FLT3 aberrations in a series of Korean APL patients. We assayed FLT3 ITD and D835 mutation status in 75 newly diagnosed APL patients and we correlated the presence of these mutations with clinical parameters and outcomes. Of the 75 patients, fifteen (20.0%) carried FLT3 mutations, nine (12.0%) with FLT3 ITD, seven (9.3%) with D835 mutations and one with both types. Patients presenting with higher leukocyte counts (>10×109/L) had a significantly higher frequency of FLT3 ITD (P = 0.030). There was no association between FLT3 aberrations and other clinicohematologic features including age, gender, M3 variant morphology and PML/RARα subtype. Death at presentation before induction chemotherapy was significantly more frequent in patients with ITD than in those without ITD (33.3% vs. 4.5%, P = 0.020), but was not significantly related to the presence of D835 mutations (28.6% vs. 5.9%, P = 0.094). Both ITD and D835 mutations were associated with shortened event-free survival (P = 0.048 and P = 0.029, respectively), but there was no correlation between disease-free survival among the 61 patients who achieved complete remission and the presence of FLT3 mutations (P = 0.543 for ITD and P = 0.277 for D835). FLT3 mutations were less frequent in Korean APL patients than in Western APL patients. In Korean patients, however, FLT3 mutations were associated with higher leukemic burdens and early deaths before remission resulting in inferior prognosis.