JAK2 V617F

The results of multivariate Cox regression analysis showed that TET2 mutation (HR=8.483, 95%CI: 1.278-56.330) was a risk factor of SMF in JAK2V617F+ MPN patients. TET2 mutation is a risk factor for SMF in JAK2V617F+ MPN patients.

The signature of CAL effects is detected in the bone marrow progenitors of patients with myeloid malignancy or severe infection. These results position CAL as a mediator of IL6 effects on triggering anemia during inflammation, an effect that is amplified in the context of JAK2-V617F-driven hematopoiesis.

 The present findings suggest that circulating factors in MPNs with SVT debut induce endothelial proinflammatory and prothrombotic phenotypes, which are modulated in vitro with MPN treatment.

Additionally, the patient responded well to a bortezomib-based treatment regimen, despite the absence of specific therapy for ET. We believe that our findings add new understanding to these rare diseases and encourage further research in this area.

P2, N=110, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Dec 2025

The patients with both JAK2 and FVL mutations had a higher incidence of thrombotic events than those with JAK2 but without FVL mutations. The relative risk ratios for increased risk for thrombotic events among patients with MPDs were 2.1 and 4.3 for patients with JAK2 mutations alone and those with JAK2 and FVL mutations, respectively. Further larger prospective studies are warranted.

 The presence of the JAK2-V617F mutation, regardless of allele burden, and prior thrombosis were strongly associated with an increased risk of VTE. Patients with prefibrotic MF might be considered at high risk for developing ATE.

The immunophenotype and the landscape of cooperative gene alterations in AML with RUNX1::CBFA2T2 resemble those of AML with RUNX1::RUNX1T1, including expression of CD19, cooperative gene alterations in signaling pathway (JAK2), epigenetic/chromatin and cell cycle regulation (TET2, SMC3, and CDKN2A/B), and additional chromosomal abnormalities (trisomies 8 and 15). This case study provides insights into the pathogenesis of this rare subtype of AML.

P=N/A, N=120, Recruiting, University Hospital, Bordeaux | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Identification of germline predisposition is essential to understanding the pathogenesis of disease, impact on families, and opportunities for preventive care. Continued research is essential to further characterize the penetrance of these conditions, and how best to monitor, treat and optimize management for these families.

The consideration of such inherited traits is crucial for clinical management of patients, particularly with regards to indication for allogeneic hematopoietic cell transplant (allo-HCT) and donor selections. Herein, we describe the very instructive case of a 49-year-old woman diagnosed with JAK2 V617F-positive primary myelofibrosis (PMF) who was found to also carry a germline variant in the SH2B3 gene, detailing clinical management, donor selection process for allo-HCT purposes, and appropriate genetic counseling.

Finally, current efforts of generating novel endpoints for clinical trials aim more at disease modification and overall survival than at improvements of splenomegaly or symptoms. Together, the new generations of clinical trials promise to offer substantial improvements in the management of MF patients and long-term disease control.