ASXL1 mutation

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.

Since then, four other tyrosine kinase inhibitors (TKIs), dasatinib, nilotinib, bosutinib and most recently asciminib, have garnered approval for frontline management of CML-CP. With limited prospective comparisons between the 2G-TKIs and similar survival outcomes with imatinib compared to 2G-TKIs, the selection of a TKI for patients with newly diagnosed CML-CP must be individualized to the needs of that specific patient. Important factors to consider when choosing a drug include patient related factors (age, comorbidities, lifestyle considerations, quality of life, patient preferences, shared-decision making and whether treatment free remission [TFR] is a goal), disease related factors (risk stratification, transcript type, presence of high risk gene mutations such as ASXL1) and drug related factors (major molecular response rates with each TKI, adverse events, rates of treatment discontinuation and TFR rates).

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.

P1, N=20, Completed, University of Nebraska | Active, not recruiting --> Completed | Trial completion date: Aug 2027 --> Mar 2025 | Trial primary completion date: Oct 2026 --> Mar 2025

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.

While no significant associations were found between CH and cardiovascular disease or overall cytopenias, CH was correlated with a higher prevalence of osteoporosis, and high-risk CH was associated with cytopenias. Although not statistically significant (p = 0.09), survival curves suggested a potential trend toward higher mortality among patients with clonal hematopoiesis, supporting the need for further investigation in larger cohorts.

Notably, we demonstrate that the leukemogenic role of EVC/EVC2 is mediated through MYC pathway activation, independent of their canonical role in Hedgehog signaling. Collectively, our findings demonstrate an oncogenic event of overexpressed EVC/EVC2, identifying novel therapeutic vulnerabilities in AML.

Notably, SETBP1 mutation plays a dominant role in establishing a stable chromatin accessibility landscape, even when co-occurring with ASXL1. Our study establishes an iPSC-based model of GATA2 deficiency, offering new insights into myeloid disease progression and a platform for testing future therapeutic strategies.

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.

In a patient with R/R AML carrying an in-frame bZIP-mutated CEBPA, NR and disease progression occurred after one cycle, but elevated white blood cell (WBC) counts declined after treatment initiation and lasted for 2 weeks. These findings suggest that combining gilteritinib with venetoclax may reduce tumor burden in R/R AML/MDS patients with wild-type FLT3.

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

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.