RUNX1 together with DAT mutations predicted poor outcome in acute myeloid leukemia

Abstract

We retrospectively explored the prognostic impact of DAT mutations at diagnosis in 122 RUNX1^mut AML patients. RUNX1 missense mutation was dominant in the RUNT domain, and frameshift mutation was dominant in the TAD domain. DAT mutations occurred in 38.5% of RUNX1^mut AML. After propensity score matching, DAT^pos patients had worse two-year relapse-free survival (RFS) than DAT^neg patients (p = .041). Moreover, RUNX1^high (VAF ≥ 37.6%) patients showed poorer two-year overall survival (OS) and RFS than RUNX1^low (VAF < 37.6%) patients (OS, p = .033; RFS, p = .027), especially in the RUNX1^highDAT^pos group. Additionally, multivariate analysis confirmed that DAT mutations at diagnosis were an independent adverse factor for RFS. There were no significant differences in two-year OS and RFS between DAT^pos and DAT^neg patients or between RUNX1^high and RUNX1^low patients who undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Collectively, DAT mutations at diagnosis were adverse factors for RFS, and allo-HSCT could likely improve the poor outcomes of these patients.

Keywords:

• Acute myeloid leukemia
• RUNX1 mutation
• DAT mutations
• allo-HSCT

Author contributions

Hongjie Shen, Depei Wu and YangXu designed the research study. Jinyan Xiao, Danjun Xie, Biqi Zhou and Yujie Liu wrote the paper. Jinyan Xiao, Danjun Xie, Yujie Liu and JingLu analyzed the data. Jinyan Xiao, Jundan Xie, Yujie Liu, Jing Lu, Airui Jiang, Hong Yao, Qiaocheng Qiu, Zixuan Ding, Shengli Xue, Xiaowen Tang, Huiying Qiu and Suning Chen Performed the research. Jinyan Xiao, Danjun Xie, Airui Jiang, Hong Yao, Qiaocheng Qiu and Zixuan Ding provided molecular and clinical data. Biqi Zhou, Hongjie Shen and Yang Xu reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part by grants from the National Natural Science Foundation of China [81730003, 81870120, 82070187], the Social Development Project of Jiangsu Province [BE2019655], the Jiangsu Province Key R&D Program [BE2019798], the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the National Key Research and Development Program [2017ZX09304021, 2017YFA0104500, 2019YFC0840604].