ASXL1 mutation

Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM...Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era...Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.

Mutations in ASXL1, SRSF2, EZH2 and NRAS were significantly more frequent in RUNX1-mutated patients compared with those without RUNX1 mutations (adjusted p < 0.05). RUNX1-mutated patients exhibited poorer overall survival (median OS 18 months vs. 51 month, p < 0.001), while U2AF1 co-mutations were associated with a relatively better prognosis (median OS 34 months vs. 17 months, p = 0.003), indicating a potential modifying effect of U2AF1 on the outcome of RUNX1-mutated patients.

CH is associated with cardiometabolic outcomes and may exhibit heterogeneity across mutations and clinical phenotypes, supporting its role as a somatic genomic marker of cardiometabolic risk. However, cautious interpretation and further study are required, as CH definitions were heterogeneous. (Association of Clonal Hematopoiesis with Type 2 Diabetes and Cardiovascular Disease: A Systematic Review and Meta Analysis; CRD420251156288).

BAP1 knockdown across multiple myeloid leukemia cell lines selectively decreased HLA-E and IFN-γ-R1 expression in ASXL1-mutant backgrounds. These findings suggest that BAP1 may contribute to the regulation of IFN-γ responsiveness and immune evasion in myeloid leukemia.

In this Indian CML cohort, somatic mutations were prevalent in TKI-resistant disease, linked to advanced phase and clonal complexity, and demonstrated a non-significant trend toward lower early MMR at diagnosis, highlighting the importance of genomic testing in this context.

Categorizing patients on the basis of MR gene mutations revealed that the inferior survival of sole +8 patients may be attributed to the high frequency of MR gene mutations in these patients. These findings indicate the importance of genetic mutations, specifically MR genes, in sole +8 AML.

In addition, rare germline variant association analysis revealed that germline variation in ASXL1 had the strongest association with lung cancer susceptibility among all solid tumors. Collectively, our findings support a model in which smoking-associated expansion of ASXL1-mutant clones contributes to lung cancer development and suggest that gene-specific CHIP metrics may enhance risk stratification and early detection strategies.

Collectively, this study demonstrates that ASXL1-mutated AML is not a monolithic high-risk entity. The ImmuScore provides a biologically informed and clinically feasible tool to identify truly high-risk ASXL1-mutated patients, potentially guiding personalized therapeutic strategies.

Treatment strategies included supportive care, interferon, hydroxyurea, and ruxolitinib. PMF and SMF demonstrate distinct clinical phenotypes despite sharing bone marrow fibrosis as a common endpoint. The mutational landscape highlights the genetic heterogeneity of MF and underscores the importance of integrating clinical, pathological, and molecular information to improve disease characterization and guide individualized management.

Flow cytometry antibody indicators can suggest that MDS patients are prone to gene mutations related to chromatin regulation, transcriptional regulation, poor prognosis and leukemia transformation. The proportions of CD25+ T cells and lymphocytes were both closely related to the T-bet and GATA3 gene mutations.

In this real-world cohort, CHIP, particularly TET2 mutations, was associated with prolonged ICI treatment duration. These findings suggest that CHIP may serve as a potential biomarker for predicting the clinical benefit of ICIs in advanced solid tumors.

Core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21)(q22;q22)/RUNX1::RUNX1T1 is typically considered as a favorable-risk AML in the context of cytarabine-based intensive chemotherapy...Here, we report the case of a young patient diagnosed with CBF-AML and RUNX1::RUNX1T1 fusion gene, carrying a rare and complex three-way t(8;11;21)(q22;q13;q22) translocation, with mutated KIT, ASXL1 and TET2 genes, transforming into an aggressive and multi-refractory mediastinal myeloid sarcoma. This case illustrates that this scarcely reported variant might negatively impact the favorable prognosis of CBF-AML.