TET2 mutation

Given the patient's advanced age and underlying MF, two cycles of a low-intensity chemotherapy regimen primarily based on the "VP regimen (Vincristine + Prednisone) combined with Azacitidine" were administered...Patient tolerability to intensive chemotherapy and novel targeted agents (e.g., Venetoclax) is poor, leading to a dismal prognosis...This case not only serves as a unique model illustrating the complex evolution of a malignant clone but also profoundly reveals the unique therapeutic challenges and extremely poor survival outcome resulting from the convergence of advanced age, MF background, and MPAL transformation. It offers pivotal real-world evidence for the clinical management of this specific patient population and highlights the need to explore novel therapeutic strategies.

The risk for a second cancer was mainly observed in DNMT3A-, TET2-, SRSF2-, or JAK2-mutant CHIP. These findings suggest increased awareness of second cancer risk among patients with primary cancer and pre-diagnostic CHIP.

Integrating the activity score with the clinical models substantially improves prediction of incident cytopenia, myeloid neoplasm, and major adverse cardiovascular events. These findings establish that TET2 and DNMT3A CHIP pathogenicity is proportional to the degree of enzymatic disruption conferred by specific variants, and nominate methylation-based activity scores as a functional biomarker for individualized CHIP risk stratification and monitoring therapeutic response.

These findings provide mechanistic insight into how aberrant DNA methylation drives HSC dysfunction in MDS and offer an epigenomic resource for discovering regulators and therapeutic targets at the stem cell level. The online version contains supplementary material available at 10.1007/s44466-026-00034-4.

Not available.

Mutation burden is a key determinant of IST response, while TP53 and DNMT3A mutations signal poorer long-term outcomes. Mutational profiling may improve risk stratification and guide personalized management.

For management, we evaluate conventional therapies (corticosteroids, etoposide) and emerging immunomodulatory agents (anakinra, ruxolitinib, emapalumab), emphasizing the 2023 treatment regimen by the American Society of Transplantation and Cellular Therapy (ASTCT). By integrating risk stratification, early diagnostic criteria, and tailored therapeutic approaches, this review aims to improve clinical outcomes for IEC-HS patients.

Many of the mutations described implicate driver mutations in advanced-stage MF and have been associated with poor survival. While there is no evidence suggesting a singular mutation for the pathogenesis of LCT, the constellation of mutations may be responsible for histologic progression to LCT.

In contrast, majority of BCL6 translocations in thyroid EMZL juxtaposed the BCL6 gene to the IGHJ/D region without encompassing the Eμ enhancer or its partner genes in an opposite orientation, thus less likely to lead to constitutive BCL6 transactivation. The above genetic changes likely dysregulate B-cell maturation and peripheral tolerance, thus offer significant molecular insights into the pathogenesis of thyroid lymphomas, particularly underpinning autoimmunity in the lymphomagenesis and potentially explaining the overlap in histopathology between EMZL and FL.

This represents the first documented case of the sequential transformation across three distinct lymphoid malignancies attributable to a germline TET2 mutation, underscoring its pivotal role in lymphomagenesis and clonal evolution. The online version contains supplementary material available at 10.1007/s00277-026-06930-4.

P2, N=80, Recruiting, Mayo Clinic | Trial completion date: Mar 2027 --> Nov 2033 | Trial primary completion date: Mar 2027 --> Feb 2031