TET2 mutation

Single-cell analysis showed FASN, SETD5, and KDM5B are expressed predominantly in malignant cells, whereas KMT2C and TET2 are not, indicating cell-type heterogeneity. De novo lipogenesis upregulation is the most consistent lipid alteration in high-grade central chondrosarcoma, nominating SQLE, ACACA, and FASN as candidates for experimental investigation.

Cases harboring biallelic TET2 inactivation or TET2+SRSF2 co-mutation show the highest bone marrow monocyte burden, frequent classical monocyte (MO1; CD14+/CD16-) elevation, and highest progression risk representing biologically true OM-CMML, whereas SF3B1-mutated and biallelic TP53 mutated cases show MDS-directed biology and warrant reclassification. This review synthesizes current diagnostic frameworks, molecular heterogeneity, risk stratification approaches, and evolving classification proposals, thereby providing a practical guide for pathologists navigating OM-CMML in the modern genomic era.

Outcomes appear to be influenced by an interplay of disease context, clonal architecture, and therapeutic strategy rather than individual mutations alone, underscoring the need for integrated molecular profiling and prospective studies to guide management. This study highlights that MS with MR mutations may follow different cellular pathways to evolution.

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).

Although limited by its retrospective character, small sample size and incomplete molecular data, this study shows that long-term survival after allo-HCT is achievable in patients with MDS/MPN with Neutrophilia, particularly in younger individuals with low disease burden. However, relapse and NRM remain major challenges underscoring the need for optimized post-transplant strategies.

Together, these findings suggest that hematopoietic clones harboring specific mutations may act as upstream regulators of chronic inflammation and carcinogenesis within the GI tract. This review consolidates gene-specific mechanisms, interactions with the gut-liver immune axis, and implications for targeted interventions linking CHIP with gastrointestinal inflammation, fibrosis, and malignancy.

We leveraged the Phase III Fondazione Italiana Linfomi FOLL12 trial, which treated patients with advanced-stage FL with R-CHOP or R-Bendamustine, to evaluate the role of myeloid CH at baseline and after chemoimmunotherapy (CIT). Patients acquiring fit DDR clones (N = 37) had inferior long-term outcomes, including independent increased risk of second malignancies (hazard ratio [HR] 2.63, P = 0.035) that developed in 28 patients, and shorter OS (HR 3.28, P = 0.008). CH emerges as a novel and potentially valuable biomarker in FL, capable of predicting long-term toxicities that are key endpoints in indolent lymphoid malignancies characterized by long-lasting survival.

Despite standard induction and intrathecal chemotherapy, bone marrow assessment demonstrated primary refractory disease. This case highlights aggressive secondary AML with adverse biology, CNS involvement, and induction failure.

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.

P2, N=25, Suspended, Abhay Singh, MD MPH | Recruiting --> Suspended

This case establishes the shared clonal origin between AITL and BL arising in the setting of CH and provides additional biological insight into the development of B-cell lymphoma associated with AITL.