ASXL1 mutations
Current understanding
ASXL1 mutations are high-risk lesions in PMF associated with reduced survival and adverse prognosis in the MIPSS70 risk score.
Evidence log
- 2026-10-07 — Outcome heterogeneity in CALR-mutated myeloproliferative neoplasms.: In this CALR-mutated MPN outcome analysis, TP53, KRAS, and RUNX1 emerged as the dominant HMR co-mutations driving adverse LFS/OS, situating ASXL1 within a broader expanded HMR panel in the CALR subset. (novelty: 3)
- 2026-07-01 — Genomic profiling for decision-making in post-polycythemia vera and post-essential thrombocythemia myelofibrosis.: In post-PV/post-ET myelofibrosis, ASXL1 mutations combined with the UTS (U2AF1/TP53/SRSF2) signature refine MYSEC-PM into MYSEC-mPM/MYSEC-kmPM scores that significantly improve overall-survival prediction, cementing ASXL1’s adverse prognostic weight specifically in the secondary MF setting. (novelty: 3)
- 2026-08-12 — Additional myelodysplasia-related gene mutations alter clinical presentation and worsen prognosis in patients with/co-mutated myeloid neoplasms.: In TET2-co-mutated myeloid neoplasms, ASXL1 is the most common additional myelodysplasia-related gene mutation and drives reduced monocytosis, increased anemia, ~50% reduction in overall survival, and higher CMML-to-AML transformation, reinforcing ASXL1’s dominant adverse prognostic weight even within TET2-mutant backgrounds. (novelty: 3)
- 2026-07-23 — DNMT3A and TET2 Mutations are Associated With Both Venous Thrombosis and Major Bleeding in Patients With Polycythemia Vera and Essential Thrombocythemia.: In the same MPN cohort where DNMT3A and TET2 mutations were tied to thrombosis and bleeding in PV/ET, ASXL1 was profiled alongside as a comparator high-risk epigenetic-regulator mutation, helping delineate which non-driver lesions specifically modify hemostatic (versus prognostic/progression) risk. (novelty: 3)
- 2026-07-31 — Unmasking Additional Mutations: A Single Institution Study in Myeloproliferative Neoplasms.: Retrospective NGS cohort confirms ASXL1 among the high-molecular-risk co-mutations recurrently unmasked by comprehensive 75-gene profiling at MPN diagnosis, supporting routine inclusion of ASXL1 in baseline risk stratification. (novelty: 3)
- 2026-07-13 — Mutational profile and cardiovascular risk factors impact prognosis in triple-negative essential thrombocythemia.: In triple-negative ET, pathogenic ASXL1 mutations (alongside CBL, EZH2, ZRSR2) predicted leukemic progression and worse overall survival, extending ASXL1’s high-risk prognostic role into the driver-mutation-negative ET subset. (novelty: 3)
- 2026-08-18 — Immune and cytokine landscape differs between cytopenic and proliferative phenotypes in primary myelofibrosis.: Cytopenic PMF is enriched for high-molecular-risk mutations including ASXL1, linking ASXL1’s adverse prognostic profile to a biologically distinct NF-κB-inflammatory, cytokine-skewed disease phenotype. (novelty: 3)
- 2026-03-09 — Clonal Architecture of ASXL1-mutated Myelofibrosis: Prospective study characterizes the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis and confirms its prognostic significance, reinforcing ASXL1’s high-risk status with architecture-level resolution. (novelty: 3)
- 2026-04-27 — Clinical Impact of Next-Generation Sequencing-Detected Mutations on Thrombotic Events in Myeloproliferative Neoplasms.: NGS profiling of 91 MPN patients linked ASXL1 mutations to arterial thrombotic events, bone marrow fibrosis, and inferior overall survival, extending ASXL1’s high-risk profile to include arterial thrombotic risk. (novelty: 3)