SRSF2 mutation

This work provides the first genomic characterisation of a diagnosed MDS cohort in China and establishes the first risk prediction model for MDS-to-AML transformation, alongside novel prognostic models for OS and PFS. These tools offer improved prognostic prediction and potential guidance for therapeutic strategies in Chinese patients with MDS.

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.

The inflammatory effects and their response to treatment were recapitulated in human hematopoietic stem and progenitor cells (HSPC). Collectively, our findings showed a pathogenetic link between SRSF2P95H and cGAS-STING activation in CMML and its vulnerability to therapeutic intervention.

OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

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.