Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients

Background Internal tandem duplications of the FLT3 gene ( FLT3 -ITDs) are frequent in patients with acute promyelocytic leukemia (APL), however its clinical impact remains controversial. Design and Methods We analyzed the prognostic significance of FLT3- ITD mutant level and size, as well as FLT3 -D835 point mutations, PML-RARα expression and other predictive factors in 129 APL patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86) PETHEMA trials. Results FLT3-ITDs and D835 mutations were detected in 21% and 9% of patients, respectively. Patients with increased ITD mutant/wild-type ratio or longer ITD size displayed shorter 5-year relapse-free survival (RFS) ( P =0.048 and P 10×109/L) ( P =0.018) were independent predictors for shorter RFS. We identified a subgroup of patients with high WBC, long FLT3 -ITD and low NCN of transcripts that showed an extremely bad prognosis (5-year RFS 23.4%, P <0.0001). Conclusions In conclusion, FLT3 -ITD size and PML-RARα transcript levels at diagnosis could contribute to improve the risk stratification in APL.