ASXL1 mutation

P=N/A, N=10, Not yet recruiting, The Second Medical Center of Chinese PLA General Hospital​; The Second Medical Center of Chinese PLA General Hospital?

TP53-mutated AML with VAF < 10% may represent a biologically distinct subgroup. Further multicenter studies with larger cohorts are needed to validate and refine the VAF threshold for prognostic evaluation and individualized management.

P=N/A, N=90, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting

Our study demonstrates that patients with eAML subtype have a worse prognosis, unique molecular features and higher tumor burden. Allo-HSCT might be an effective way to improve prognosis. This study provides evidence critical for risk stratification and treatment optimization in eAML.

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.

P1, N=12, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting

MRD of secondary type mutations alone lacks predictive value, yet MRD of non-DTA mutations in CR is associated with increased CIR in st-AML (SHR MRDpos vs. MRDneg 3.25; p<0.001). Molecularly-defined st-AML, including st-MDS/AML, defines a distinct AML category with a unique genetic, clinical and treatment response profile, in which NGS-based MRD holds markedly prognostic significance.

Emerging therapeutic strategies, including inflammasome inhibition, STING modulation, and epigenetic restoration, highlight its potential as a modifiable risk factor. This narrative review synthesizes current epidemiological, mechanistic, and translational insights, framing CHIP as an emerging causal factor in cardiometabolic disease and as a promising target for precision medicine in aging populations.

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.

Variant rs17834140-T was associated with slower CH expansion, and stem cell MSI2 levels modified ASXL1-mutant HSC clonal dominance. These findings leverage natural resilience to illuminate posttranscriptional regulation in human HSCs, suggesting that inhibition of MSI2 or its targets could be rational strategies for blood cancer prevention.

BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.