1254 Reassessing the Clinical Impact of RUNX1 Mutations in Acute Myeloid Leukemia in a Population-Based Comparative Study

Document Type

Conference Proceeding

Publication Date

3-23-2026

Publication Title

Lab Invest

Keywords

acute myeloid leukemia, adult, aged, clinical article, comparative study, conference abstract, controlled study, drug combination, drug therapy, female, genetic risk, high risk population, human, male, myelodysplastic syndrome, overall survival, treatment response

Abstract

Disclosures: Hira Qadir: None; Kedar Inamdar: None; Sharmila Ghosh: None; Yulei Shen: None; Juan Gomez-Gelvez: None; Elizabeth Wey: None; Philip Kuriakose: None; Wei Liu: None Background: RUNX1 mutations are myelodysplasia-defining in AML in International Consensus Classification (ICC22), but not in the 5th edition World Health Organization Classification (WHO22). Additional data is needed to better define the role of RUNX1 mutations in AML. Design: AML cases harboring RUNX1 mutations (AML-RUNX1mut) were extracted from a population-based database containing 172 consecutive AML patients (2018-2022). They were compared with two WHO22 groups (excluding cases with RUNX1 mutations): 1. AML-myelodysplasia-related (AML-MR); 2. AML defined by differentiation (AML-diff). Clinical impact was assessed in correlation with ELN2022 genetic risk stratification, post-induction therapy response and overall survival (OS). Results: 18 AML-RUNX1mut cases (10.4%; median age 66, M/F=1.3:1) were extracted, with 8 from AML-diff (AML-diff-RUNX1mut) and 10 from AML-MR (AML-MR-RUNX1mut) under WHO22, and 17 AML-MR and 1 AML-TP53 under ICC22. AML-diff-RUNX1mut and AML-MR-RUNX1mut showed differential cytogenetic and mutational profiles (data not included). While 100% AML-RUNX1mut (n=18) classified as adverse risk group by ELN2022 (vs. 7.1% AML-diff [n=28, p<0.0001]; vs 92.9% AML-MR [n=56, p=0.57]), AML-RUNX1mut (n=14) appeared with a post-induction treatment non-response rate (NRR) (50%) in between those (27.8% and 65.2%) in AML-diff (n=18) and AML-MR (n=23) (p<0.05). Similarly, OS in AML-RUNX1mut (n=16) was significantly longer than that of AML-MR (n=56; 532 vs 117 days, p<0.05), and shorter than that of AML-diff (n=28) despite no statistical significance (532 vs 1603 days, p=0.53). With further stratification, AML-diff-RUNX1mut (n=6) and AML-MR-RUNX1mut (n=8) displayed significantly different treatment NRR (0% vs. 87.5%, p<0.005), while respectively similar to those of AML-diff and AML-MR (0% vs. 27.8% [p=0.28] and 87.5% vs. 65.2% [p=0.38]). Additionally, despite no significant difference in OS between AML-diff-RUNX1mut (n=6) and AML-MR-RUNX1mut (n=10), AML-diff-RUNX1mut, like AML-RUNX1mut, showed significantly longer median OS than that of AML-MR (532 vs. 117 days, p<0.05), with no significant difference than AML-diff. Conclusions: AML-RUNX1mut is a heterogeneous group with intermediate post-induction treatment responses and overall survivals between AML-diff and AML-MR under WHO22, within which AML-diff-RUNX1mut and AML-MR-RUNX1mut appear different with similar treatment responses and overall survivals to AML-diff and AML-MR respectively.

Volume

106

Issue

3

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