FENG-MING TIENCHENG-HONG TSAIHuang, Sheng-ChuanSheng-ChuanHuangJIA-HAU LIUChen, Chien-YuanChien-YuanChenYUAN-YEH KUOChuang, Yi-KuangYi-KuangChuangTseng, Mei-HsuanMei-HsuanTsengPeng, Yen-LingYen-LingPengLiu, Ming-ChihMing-ChihLiuCHIA-WEN LIULiao, Xiu-WenXiu-WenLiaoLIANG-IN LINWu, Yu-SinYu-SinWuHou, Mei-FangMei-FangHouSHANG-JU WUSZU-CHUN HSUBOR-SHENG KOWEN-CHIEN CHOUMING YAOHSIN-AN HOUJIH-LUH TANGHWEI-FANG TIEN2023-01-162023-01-162022-010268-3369https://scholars.lib.ntu.edu.tw/handle/123456789/627255The mutant burden of FLT3-ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3-ITD (FLT3-ITDlow, AR < 0.5), clinical features, as well as genomic and transcriptomic profiles remain unclear, and evidence supporting allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains controversial. This study aimed to elucidate the genomic features, prognosis, and transplantation outcome of FLT3-ITDIow in AML patients with intermediate-risk cytogenetics. FLT3-ITDlow was associated with a negative enrichment of the leukemic stem cell signature, a marked enrichment of the RAS pathway, and with higher frequencies of RAS pathway mutations, different from those with FLT3-ITDhigh. Concurrent CEBPA double mutations were favorable prognostic factors, whereas MLL-PTD, and mutations in splicing factors were unfavorable prognostic factors in FLT3-ITDlow patients. Patients with FLT3-ITDlow had a shorter overall survival (OS) and event-free survival (EFS) than those with FLT3wt. Allo-HSCT in CR1 was associated with a significantly longer OS and EFS compared with postremission chemotherapy in patients with FLT3-ITDlow. In conclusion, FLT3-ITDlow is associated with different mutational and transcriptomic profiles compared with FLT3-ITDhigh. The presence of concomitant poor-risk mutations exert negative prognostic impacts in patients with FLT3-ITDlow, who markedly benefit from allo-HSCT in CR1.enACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; 2017 EUROPEAN LEUKEMIANET; NPM1 MUTATION; RISK-STRATIFICATION; PROGNOSTIC IMPACT; ADULT PATIENTS; SURVIVAL; DNMT3A; LEVELjournal article10.1038/s41409-021-01454-z346711202-s2.0-85117375512WOS:000709266900003