Distinct clinico-biological features in AML patients with low allelic ratio FLT3-ITD: role of allogeneic stem cell transplantation in first remission
Journal
Bone marrow transplantation
Journal Volume
57
Journal Issue
1
Pages
95-105
Date Issued
2022-01
Author(s)
Huang, Sheng-Chuan
Chuang, Yi-Kuang
Tseng, Mei-Hsuan
Peng, Yen-Ling
Liu, Ming-Chih
Liao, Xiu-Wen
Wu, Yu-Sin
Hou, Mei-Fang
Abstract
The 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.
Subjects
ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; 2017 EUROPEAN LEUKEMIANET; NPM1 MUTATION; RISK-STRATIFICATION; PROGNOSTIC IMPACT; ADULT PATIENTS; SURVIVAL; DNMT3A; LEVEL
Publisher
SPRINGERNATURE
Type
journal article