Myeloproliferative Neoplasm

P1, N=220, Recruiting, Janssen Research & Development, LLC | N=100 --> 220

MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients...Elevated levels of circulating RANTES correlated with ET plasma-induced proplatelet formation, which was partially reverted by RANTES receptor CCR5 antagonist Maraviroc, indicating RANTES is involved in this process. These findings indicate that, in addition to clonal mutations, extrinsic inflammatory mediators play a direct role in MF and ET megakaryocyte abnormalities. The distinct cytokine profile could potentially be useful for the development of targeted therapies.

In addition, we assessed the effect of gene polymorphisms on the course of the disease, and rapid disease progression was found to be correlated with the presence of these polymorphisms. These findings could help determine the risk of developing MPNs and patient prognosis.

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.

Statistically significant interactions existed between COPD/asthma, female sex (HR 3.94, 95% CI 1.01-11.02), ET phenotype (HR 7.1, 95% CI 15.3-16.7), JAK2 positive status (HR 4.17, 95% CI 1.04-6.9), hydroxyurea use (HR 4.67, 95% CI 1.10-7.43), and the presence of other cardiovascular risk factors (HR 8.1, 95% CI 1.55-10.72) with overall thrombotic risk (interaction p < 0.050 for all analyses)...There was no effect of COPD/asthma on overall survival. These results provide an important signal regarding the potentially inferior outcomes in ET/PV patients presenting with these common respiratory disorders and may help to further personalize MPN management.

Modulating the miR-122-5p/CDC25A axis may provide potential molecular targets for inhibiting CML progression through regulation of cell cycle pathways. Findings are exploratory and based on bioinformatics with limited in vitro expression confirmation; functional studies are required to establish causality.

One of the mutations that is still an on-going challenge in clinical and scientific field is the T315I mutation, since it gives patients a poor prognosis attributable to acquired resistance to therapy. In the following narrative review, we will discuss the current knowledge on the T315I mutation, explore the most suitable treatment options, examine the role of third-generation tyrosine kinase inhibitors, and outline potential future therapeutic strategies.

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Suspended --> Recruiting

P1, N=34, Active, not recruiting, City of Hope Medical Center | Trial completion date: Aug 2025 --> Jul 2026

These findings establish OSM as a key mediator linking oncogenic STAT5 activation to remodeling of the microenvironment and immune suppression. Targeting OSM signaling therefore represents a promising therapeutic strategy to alleviate disease progression in myeloproliferative neoplasms and related malignancies.

This demonstrated that the spatial distribution of the marginal zone, red pulp and white pulp remained unaltered upon anti-integrin treatment in JAK2-V617F knock-in mice. In summary, the present study identified a previously unrecognized role of the β1-integrin VLA-4 and of β2-integrin chains in extramedullary erythropoiesis of the spleen in JAK2-V617F-induced disease.

P1, N=23, Recruiting, University of Virginia