SF3B1 mutation

This review synthesizes the recent literature and critical studies validating these classification and prognostic updates, discussing their clinical impact, practical considerations, and implications for targeted therapeutic strategies. By focusing on molecular pathogenesis, the latest classification systems and prognostic models promise significant advances in patient-specific management, setting the stage for future innovations in treatment and improved patient outcomes.

Using all extracted tissue features, we developed a composite spatially informed "MDS severity score", which aligned with clinical and genetic parameters across serial samples. This work uncovers previously unrecognized, genotype-linked microarchitectural alterations in MDS, the measurement of which may enhance existing diagnostic and disease monitoring strategies.

Our results link replication stress, kinase signaling, and RNA processing across genetically diverse clonal states, highlighting potential therapeutic approaches at these nodes. While most splicing changes differ by splicing factor (SF) mutation, certain retained introns are common across subtypes.Changes in RI are bidirectional, concordant across mutant groups, and mirrors SRSF1 loss.SF mutations activate DDR, triggering an AMPKα/AKT imbalance that culminates in SRSF1 hypophosphorylation.Relieving R-loop induced DDR restores SRSF1 phosphorylation and reverses RI.

The complexity of AML was influenced by various cytogenetic and molecular abnormalities, which contributed to patients' heterogeneous presentation and survival outcomes. In addition to the previous data, IDH1, IDH2, and DNMT3A mutations might have affected survival outcomes in AML patients in our retrospective cohort. However, further studies with larger sample sizes are needed to validate these observations.

These events increase lipid peroxidation and ferroptosis susceptibility in hematopoietic cells as evidenced by enhanced BODIPY-C11 oxidation and erastin sensitivity. Our findings reveal a spliceosome-to-chromatin-to-metabolism pathway in which SF3B1 mutations promote ferroptosis through BRD9-mediated chromatin dysregulation, highlighting the previously unrecognized metabolic rewiring in myeloid malignancies.

P=N/A, N=96, Not yet recruiting, The First Affiliated Hospital, College of Medicine, Zhejiang University; The First Affiliated Hospital, College of Medicine, Zhejiang University

These findings elucidate the transcriptional dynamics underlying venetoclax resistance and propose alternative therapeutic strategies targeting BRD4 and MYB as promising avenues for improving outcomes in patients with EVI1-rearranged AML. Our work highlights the necessity for innovative combination therapies to address the multifaceted mechanisms of resistance in this high-risk leukemia subtype.

P4, N=85, Active, not recruiting, Bristol-Myers Squibb | N=60 --> 85 | Trial completion date: Apr 2026 --> Dec 2028 | Trial primary completion date: Apr 2026 --> Dec 2028

In univariate analysis, transfusion dependency was associated with poor prognosis (HR 7.78, p = 0.013). This study provides the first single-institution analysis in Korean patients with MDS/MPN and identified U2AF1 mutations as a potentially significant prognostic factor, enhancing the molecular understanding of MDS/MPN.

JAK2 VAF levels differ significantly among MPN, MDS/MPN, and MDS. MDS cases with these co-mutations had significantly poorer overall survival compared to MPN and MDS/MPN cases.