SRSF2 mutation

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.

In conclusion, SRSF2 and U2AF1 mutations are biomarkers of sensitivity to ATR-CHK1 pathway inhibitors, while RUNX1 mutations cause resistance. These biomarkers can support patient stratification in MDS/AML.

Transcriptome analyses showed that this compound causes widespread changes in gene expression in sensitive SRSF2 P95H -expressing cells. Our results demonstrate the utility of using a yeast-based HTS to identify compounds capable of changing pre-mRNA splicing outcomes.

Platelet-derived growth factor receptor beta (PDGFRB)-rearranged myeloid/lymphoid neoplasms (MLNs) are rare hematologic malignancies typically responsive to tyrosine kinase inhibitors (TKIs) such as imatinib. The patient progressed to acute myeloid leukemia (AML) within 11 months despite sequential therapies including dasatinib and azacitidine-venetoclax, ultimately succumbing to sepsis. This case highlights the limitations of TKI monotherapy in MLNs with PDGFRB rearrangements and co-existing high-risk mutations, underscoring the importance of early molecular profiling and consideration of allogeneic hematopoietic stem cell transplantation in cases with poor risk features.

CMML in patients aged 50 years and younger is rare and presents with unique clinical and mutational features, suggesting a distinct pathogenesis.

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.

Allele balance patterns suggest predominantly somatic origins for most MDS-related variants, while RUNX1 variants show enrichment consistent with germline origin. MDS is associated with elevated cardiovascular risk, whereas CHIP demonstrates no significant cardiovascular association after adjustment for demographic factors.

Low-dose dasatinib (20 mg/day) reduced BCR::ABL1 levels (FISH negative, RT-PCR positive), but had no effect on anemia, dysplasia, or transfusion frequency...In Ph-positive de novo MDS, BCR::ABL1 transcript responses alone may not reflect disease control when an adverse founder clone persists. Integrating panel-based NGS with fusion transcript monitoring may improve therapeutic decision-making and prognostic assessment.

Gene-specific prognostic patterns emerged: ASXL1, RUNX1, SF3B1, and U2AF1 mutations associated with adverse risk-like outcomes; SRSF2 and STAG2 aligned with intermediate-risk; BCOR, EZH2, and ZRSR2 did not differ significantly from intermediate or adverse risk. These findings from a large cooperative cohort highlight prognostic heterogeneity among MR mutations and suggest that SRSF2 and STAG2 mutations are associated with less adverse risk patterns, comparable to intermediate-risk.

These observations highlight the biological relevance of CHIP-associated mutations and underscore the value of post-remission molecular surveillance to detect emerging secondary neoplasms in AML survivors. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Treatment methods mainly include bloodletting therapy, low-dose aspirin anticoagulant therapy, cytoreductive therapy, and allogeneic hematopoietic stem cell transplantation (HSCT). JAK inhibitors (such as ruxolitinib) remain the basic therapeutic drugs...New methods, including combination therapy (combination of JAK inhibitors and BCL-XL inhibitors) and mutation-independent immunotherapy, are under investigation. This review summarizes the latest advancements in the diagnosis and treatment of MPNs, highlighting the importance of molecular mechanisms in guiding therapeutic approaches and the potential for precision medicine in the future.

Compared to a control cohort of 23 patients with MDS and an SRSF2 mutation, but without isolated +19 (MDS-SRSF2), the 16 MDS +19 patients with SRSF2 mutation and the 12 MDS +19 patients with an ASXL1 mutation showed a striking difference in the presence of ≥ 15% RS (73% and 67% versus 17% in MDS-SRSF2) and the occurrence of fibrosis (44% and 57% versus 4% in MDS-SRSF2). Although all individual features observed in the MDS +19 and MDS/MPN +19 cohorts are seen in MDS and MDS/MPN in general, their combination is rather unique and provides clues regarding disease evolution in this rare, cytogenetically defined group of myeloid neoplasia.