Clinical And Genetic Features Of Acute Promyelocytic Leukemia

ObjectiveWe retrospectively analyze the clinical and genetic features of 1379 acute promyelocytic leukemia(APL)patients and 17 cases of variant APL patients from the First Affiliated Hospital of Soochow University between January 2003 and December 2016.Summarize the characteristics of this special subtype of acute myeloid leukemia.Compare the basic data,therapeutic effect and prognosis of patients between classic APL and variant APL.MethodsCollect the age,gender,onset date and other basic information of APL patients from January 2003 to early December 2016.Patients'characteristics were analyzed by?2-test or Fisher's exact tests for univariate analysis.P<0.05 was considered significant.All calculations were performed using the SPSS software package(version 24.0).Karyotyping,fluorescence in situ hybridization(FISH),RNA-Sequencing,array-CGH,and whole genome sequencing were performed to identify variant fusion transcripts in APL patients lacking classical t(15;17)or PML-RARa fusion.Result1.A total of 1379 cases of APL patients were identified in our center between January2003 and December 2016,comprising 732 males and 647 females.Median age was 40years(range,4-91 years).The median white blood cell count at presentation was 2.6×10~9/l(range 0.2-200×10~9/l),hemoglobin 84g/l(range 24-162g/l)and platelets 26×10~9/l(range 1-282×10~9/l).According to the white blood cell and platelet count at diagnosis,patients could be classified into three risk groups:171(26.5%)cases of high risk,325(50.3%)cases of intermediate risk and 150(23.2%)low risk.Of the 1219 patients with available karyotypic data,992 cases(81.3%)were with t(15;17)as the sole abnormality,and 227 cases were with additional abnormalities except for t(15;17).Trisomy 8 was the most common additional chromosomal abnormality,followed by 9q-,+21,i(17q),6q-and so on.Of the 767 patients with evaluated PML-RARa fusion information,503 cases were L type,and 261 cases were S type.The propotion of patients with S type in high risk was higher than that of L type,but the overall survival between two groups was not significant.Analysis of mutations in APL patients showed that FLT3-ITD was the most frequent mutant.Of the 224 patients who underwent mutation detection,61 patients were positive with FLT3-ITD mutation,and 163 cases were negative with FLT3-ITD mutation.The mutation rate of FLT3-ITD was 27.23%,which was consistent with previous reports.2.There were 17 cases of variant APL patients in our data,comprising 16 males and only 1 female.The median age was 39 years(rage 25-70 years).The median white blood cell count was 19.7×10~9/l(range 1.34-72.7×10~9/l),hemoglobin 83 g/l(range 45-125 g/l),platelet count 78×10~9/l(range 24-282×10~9/l).There were four variants of RARa rearrangements in our study,including 10 patients with PLZF-RARa,4 cases with STAT5B-RARa,2 cases with STAT3-RARa and 1 TBLR1-RARa.Variant APL patients were more commonly in high risk group(10 cases of high risk and 3 cases of low risk).conclusion1.Acute promyelocytic leukemia was most commomly occurred in patients between30 and 50 years old,and there was no significant difference between male and female.Patients with intermediate risk accounted for more than half of the proportion.The most frequent additional chromosomal abnormalities in APL patients were:+8,9q-,+21,i(17q),6q-and so on.Patients with L type PML-RARa fusion gene were more than patients with S type.The propotion of S type patients with white blood cell count greater than 10×10~9/l was higher than that of L type patients,the hemoglobin level of patients in S type was higher than L type.Although S type patients with high risk were more than L type patients,the overall survival between two groups was not significant.FLT3-ITD was the most frequent gene mutation in patients with APL,the mutation rate is 27.23%.The proportion of white blood cell count,S-type fusion gene and high-risk group were significantly higher in FLT-ITD mutant group than in non-mutant group.The 5-year overall survival rate of FLT3-ITD mutant group was significantly lower than that of non-mutant group.2.In total 1379 APL patients,there were 17 cases of variant APL.The incidence of variant APL was about 1.3%.The proportion of male patients in variant APL was higher than that in classic APL.Compared with classic APL patients,the proportion of patients with high risk was higher in variant APL patients.Prognosis of patients with variant APL was worse than that of classic APL,and hematopoietic stem cell transplantation may improve the prognosis of patients with variant APL.