Usefulness of KIT mutant transcript levels for monitoring measurable residual disease

Yuan Sun ^{1 2}, Xu Wang ¹, Wen-Min Chen ¹, Yue Hao ¹, Ling-Di Li ¹, Jin-Ying Li ¹, Kai Sun ¹, Zong-Yan Shi ¹, Hao Jiang ¹, Qian Jiang ¹, Xiao-Jun Huang ¹, Ya-Zhen Qin ¹

Abstract

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT^mut) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT^mut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KIT^mut (D816V/H/Y or N822K) were tested for KIT^mut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT^mut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT^mut-high (KIT_H) group and the KIT^mut-low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The < 3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with > 3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4 %) had similar RFS as that of patients with < 3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT^mut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patients with KIT mutation.