RUNX1 mutation

These results were confirmed in the CBF-2006 validation cohort. KIT-TKD mutations in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.

The median overall survival was 35.1 months for AML with RUNX1::RUNX1T1 versus 24.0 months for other AML (p = 0.0797) and 28.1 months in patients with KIT mutations versus 25.6 months in those without (p = 0.9051). These data highlight a strong biological association between RUNX1::RUNX1T1 and KIT exon 17 mutations and underscore the need for prospectively designed studies and the evaluation of KIT-directed therapeutic strategies in this subset of patients with AML.

In aggregate, these findings may contribute to a better understanding of disease pathophysiology and help elucidate the role of potentially clinically relevant TGF-β signaling. This is particularly significant given the clinical use of agents targeting TGF-β-signaling such as luspatercept, as well as the emergence of several CCN2-targeting therapies currently undergoing clinical or preclinical evaluation with promising results.

This study evaluated the clinical efficacy of venetoclax and azacitidine (VEN+AZA) versus CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) for newly diagnosed adult acute myeloid leukemia (AML) unfit patients. 31.7 % (P = 0.20). Patients with age ≥ 60 y (EFS, P = 0.032), ECOG≥ 2 (EFS, P = 0.047), secondary AML (OS, P = 0.015; EFS, P = 0.039), ELN intermediate-adverse karyotype (OS, P = 0.034; EFS, P = 0.044), RUNX1 mutation (OS, P = 0.003; EFS, P = 0.003) and IDH1/2 mutation (EFS, P = 0.039) showed a preference for VEN+AZA regarding OS, and patients with SRSF2 mutation favored CAG in OS (P = 0.031).

Different induction therapies (chemotherapy/low-intensity treatment) showed no significant impact on the efficacy or prognosis of patients with RUNX1 mutations (P>0.05). Patients with concurrent RUNX1 and DNMT3A or ASXL1 mutations portend a poorer prognosis, and the cooccurrence of FLT3-ITD mutation further leads to inferior therapeutic outcomes.

Here, we present two cases of pDC-AML with B-cell marker expression in which RUNX1 aberrations were not identified. Although previously we speculated on the role of RUNX1 in the aberrant expression of B-cell markers such in cases, the absence of RUNX1 lesions in the current cases supports the potential inherent ability of pDCs to express B-cell markers during maturation.

Current research has revealed that ASXL1 mutations in MDS predict demethylating agents (HMAs) resistance, the combination of HMAs and Venetoclax (VEN) achieved an ORR of 87%. DNMT3A R882 mutations induce decitabine sensitivity via hemi-methylated enhancer trapping, and TET2 mutations enhance HMAs efficacy only in ASXL1 wild-type contexts (ORR 62.1% vs. co-mutated 19%). RUNX1 aberrations reduce chemotherapy responses (18.9% ORR in high-risk MDS) through DNA repair impairment, while BCOR/EZH2 loss drives cytarabine resistance. TP53 multi-hit lesions correlate with poor survival (OS <12 months) but respond to eprenetapopt-azacitidine (ORR 73%), and IDH1/2 inhibitors achieve durable remissions (ivosidenib ORR 83.3%, mOS 35.7 months). In this paper, we systematically illustrate the correlation between key gene mutations and the response to HMAs, chemotherapy and targeted therapies in MDS patients. This article summarizes the current evidence on gene mutations as predictive biomarkers and discusses the direction of individualized therapy.

The overall survival of MDS patients with ASXL1mut is poor. The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis. There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group. ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

Patients with RUNX1 mutations had inferior 5 year OS in multivariable analysis (p-value = 0.009). These findings suggest specific genomic alterations that may refine risk stratification and guide future therapeutic protocols in Taiwanese pediatric patients with AML.

It suggests that avapritinib may bridge therapeutic gaps for atypical KIT-mutant systemic mastocytosis with associated hematologic neoplasm (SM-AHN) that is ineligible for Allo-HSCT or relapsed. Prospective trials are warranted to validate its efficacy, optimize dosing, and explore synergies with Allo-HSCT, offering new strategies for these high-risk patients.

KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.

P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Trial completion date: Feb 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> May 2026