Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance

// Long Su 1, * , YeHui Tan 1, * , Hai Lin 1 , XiaoLiang Liu 1 , Li Yu 2 , YanPing Yang 1 , ShanShan Liu 1 , Ou Bai 1 , Yan Yang 1 , FengYan Jin 1 , JingNan Sun 1 , ChunShui Liu 1 , QiuJu Liu 1 , SuJun Gao 1 and Wei Li 1 1 Department of Hematology, The First Hospital, Jilin University, Changchun, China 2 Department of Hematology, Chinese PLA General Hospital, Peking, China * These authors have contributed equally to this work Correspondence to: SuJun Gao, email: gaosujunjdyy@163.com Keywords: acute myeloid leukemia; CEBPA mutations; next generation sequencing; prognoses; Chinese population Received: March 16, 2017     Accepted: December 27, 2017     Epub: January 03, 2018     Published: May 18, 2018 ABSTRACT The aim of this study was to profile the spectrum of genetic mutations in acute myeloid leukemia (AML) patients co-occurring with CEBPA double mutation ( CEBPA dm ). Between January 1, 2012, and June 30, 2017, 553 consecutive patients with de novo AML were screened for CEBPA mutations. Out of these, 81 patients classified as CEBPA dm were analyzed further by a sensitive next-generation sequencing assay for mutations in 112 candidate genes. Within the CEBPA gene itself, we found 164 mutations. The most common mutated sites were c.936_937insGAG (n = 11/164, 6.71%) and c.939_940insAAG (n = 11/164, 6.71%), followed by c.68dupC (n = 10/164, 6.10%). The most common co-occurring mutations were found in the CSF3R (n = 16/81, 19.75%), WT1 (n = 15/81, 18.52%), and GATA2 (n = 13/81, 16.05%) genes. Patients with CSF3R mutations had an inferior four-year relapse-free survival (RFS) than those with the wild-type gene (15.3% versus 46.8%, respectively; P = 0.021). Patients with WT1 mutations had an inferior five-year RFS compared with those without such mutations (0% versus 26.6%, respectively, P = 0.003). However, GATA2 , CSF3R , WT1 mutations had no significant influence on the overall survival. There were some differences in the location of mutational hotspots within the CEBPA gene, as well as hotspots of other co-occurring genetic mutations, between AML patients from Chinese and Caucasian populations. Some co-occurring mutations may be potential candidates for refining the prognoses of AML patients with CEBPA dm in the Chinese population.