# KIT Mutant/Core binding factor-negative acute myeloid leukemia might be a complex subgroup with dismal prognosis: a single-center retrospective analysis

## TL;DR

This study finds that KIT mutant/CBF-negative AML is a complex and high-risk leukemia subgroup with poor survival outcomes.

## Contribution

The study characterizes the clinical and molecular features of KIT mutant/CBF-negative AML, highlighting its poor prognosis.

## Key findings

- KIT mutant/CBF-negative AML patients had a median event-free survival of 15.3 months and overall survival of 24.1 months.
- KIT exon 17 mutations were associated with worse survival outcomes.
- Allogeneic hematopoietic stem cell transplantation improved survival in these patients.

## Abstract

KIT mutations are well-established as poor prognostic markers in core binding factor AML (CBF AML). However, data on KIT mutation in CBF-negative (CBF-neg) AML remains scarce. This retrospective study aimed to characterize the clinical features and outcomes of patients with KIT mutant (KIT mut)/CBF-neg AML. We conducted a retrospective study in our single center and identified non-M3 de novo AML with KIT mutations by next-generation sequencing (NGS) from January 2018 to June 2024. Core binding factor (CBF) AML or patients with underlying systemic mastocytosis were excluded. The clinical data of KIT mut/CBF-neg AML was collected and analyzed. 45 patients were enrolled in the cohort, including 3 patients with secondary AML. The median variant allele frequency (VAF) of KIT mutation was 41.2% and the most frequent comuations were CEBPA (27/45, 60%), WT1 (12/45, 26.7%) and NRAS (11/45, 24.4%). After a median follow-up of 48 months, the median event-free survival (EFS) and overall survival (OS) of the cohort was 15.3 months and 24.1 months, respectively. Patients with KIT exon 17 mutations tended to harbor an inferior EFS and OS. In conclusion, KIT mutant/CBF-neg AML was a complex subgroup with dismal prognosis and NIT might bring benefits for those patients.

The online version contains supplementary material available at 10.1007/s00277-026-06814-7.

KIT mutant/CBF-neg AML was a complex subgroup with various molecular biological features and CEBPA as most frequent comutation.

KIT mutant/CBF-neg AML harbored a dismal survival which was improved by allo-HSCT.

The online version contains supplementary material available at 10.1007/s00277-026-06814-7.