Myeloproliferative Neoplasm

P3, N=63, Completed, University Hospital, Brest | Recruiting --> Completed

NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

The CCDC6::JAK2 chimeric protein retains the CCDC6 coiled-coil domain and the JAK2 kinase domain. Dimerization of chimeric proteins through coiled-coil domains promotes JAK2 autophosphorylation leading to constitutive activation of the JAK/STAT signaling pathway.

These findings unveil therapeutic strategies to potentially prevent leukemic evolution in MPN patients by inhibiting specific cytokine signaling. Our data establish a new paradigm for clonal evolution of blood neoplasms by showing that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones independent of the primary disease.

Although the JAK1/2 inhibitor Ruxolitinib is clinically approved, its efficacy is limited by toxicity to normal cells and the development of drug resistance...Moreover, through a compound screen, followed by chemical proteomics and compound optimization, WWQ-03-012 is discovered, which selectively degrades mutant JAK2, induces primary leukemia cells death, and inhibits MPN progression through targeting DESI2 enzymatic activity in vitro and in vivo. These studies provide a novel therapeutic strategy against mutated JAK2 signaling in MPN and sAML.

Although heterozygosity alone appears insufficient to drive disease, the enrichment of this variant in our MPN cohort and its occurrence in relatively young patients support a possible low-penetrance predisposition role. Functional assays, larger case-control series, and assessment of genetic/epigenetic modifiers are needed to define pathogenicity and clinical utility.

Induction chemotherapy (cytarabine and idarubicin) initially achieved remission, but subsequent relapses led to the use of venetoclax and 5-azacytidine, which again resulted in remission. This is the first report that molecularly characterizes the HMBOX1::JAK2 fusion in a de novo AML patient. The identification of this novel alteration adds to the growing and heterogeneous molecular landscape of AML and suggests a potential new avenue for targeted therapy.

Following parathyroidectomy, the patient's hemoglobin and hematocrit levels normalized without further treatment, suggesting remission of PV. This case report and literature review highlight a possible relationship between the calcium-parathyroid hormone axis and hematopoiesis, providing insight into potential shared pathophysiological mechanisms.

Telmisartan was used as the internal standard (IS). Stability studies confirmed the analyte's integrity across multiple freeze-thaw cycles. The developed LC-MS/MS method is selective, sensitive, fully validated, and was successfully applied to pharmacokinetic studies.

These findings highlight the potential of targeting MSC-mediated pathways as a therapeutic strategy in polycythemia vera.

Pharmacological blockade of NLRP3 in fully established disease leads to regression of thrombocytosis, splenomegaly and bone marrow fibrosis. These findings suggest that NLRP3 is critical for MPN development and its inhibition represents a new therapeutic intervention for MPN patients.

The multifaceted nature of MS necessitates a multidisciplinary approach, including thorough diagnostic evaluation involving immunohistochemistry, cytochemistry, and cytogenetic analysis. Standardizing terminology and refining diagnostic and treatment algorithms through future prospective studies are vital steps toward enhancing clinical management and prognosis for patients with de novo myeloid sarcoma of the urogenital tract.