Impact of FLT-3 mutations on clinical features and response to the therapy in acute promyelocytic leukemia patients

ABSTRACT

FLT3 mutations are associated with poor outcome in acute myeloblastic leukemia [AML] patients. Only limited information is available about effects of FLT3 mutation on Acute Promyelocytic Leukemia [APL]. We investigated the prevalence and impact of FLT3 mutations on the clinical characteristics and the response to treatment in APL patients treated with arsenic trioxide [As[2]O[3]]. Blood samples were collected from 115 untreated APL patients and genomic DNA was extracted by the salting-out method. FLT3-ITD and FLT3-D835 mutations were investigated by PCR-RFLP. Mann-Whitney U test and Chi-square were used for data analysis. FLT3-ITD and FLT3-D835 mutations were detected in 16 [14%] and 13 [11%] of the patients, respectively. Both mutations were identified in two patients, so overall frequency of FLT3 mutations was estimated to be 23.5%. Patients positive for FLT3-ITD mutation had a higher rate of white cell counts [p= 0.005] and more frequent bcr3 type of PML/RARA fusion [p=0.04]. We have not found any significant association between FLT3-D835 mutation and the clinical characteristics of patients. Between the group with FLT3 Mutations and the group without, there was no significant difference in response to therapy. Complete remission induction with As[2]O[3] may be independent of FLT3 mutation status, so As[2]O[3] may be the first choice of APL especially in patients with FLT3 mutations. However, further studies on a large group of patients are necessary to confirm our findings: