Co-occurrence of KIT and NRAS mutations defines an adverse prognostic core-binding factor acute myeloid leukemia

Abstract

Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was KIT mutation (30.6%), followed by NRAS (24.2%) and ASXL1 (14.5%) mutations, which was associated with a higher number of bone marrow blasts (p = .049) and older age (p = .027). The survival analysis showed KIT mutation adversely affected the overall survival (OS) (p = .046). NRAS mutation was associated with inferior OS (p = .016) and RFS (p = .039). Eight patients carried co-mutations of KIT and NRAS and had worse OS (p = .012) and RFS (p = .034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of KIT and NRAS were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML.

Keywords:

• Core-binding factor acute myeloid leukemia
• KIT
• NRAS
• gene mutation
• next-generation sequencing
• prognosis

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This work was sponsored by grants from the National Natural Science Foundation of China [Nos. 81720108002, 81870119, 81700155, 81970146], Jiangsu Provincial Health and Family Planning Commission Medical Research Project [H2017087], and National Science and Technology Major Project [2018ZX09734007, 2017ZX09304032].