The cytotoxic and antifibrotic effects of the BCL-XL inhibitor ABT-263 (navitoclax), alone or combined with the JAK2 inhibitor ruxolitinib, were evaluated in stromal and hematopoietic contexts. Combined inhibition of BCL-XL and JAK2 produced synergistic antifibrotic and pro-apoptotic effects in MSCs, post-MPN acute myeloid leukemia (AML) cell lines, and patient-derived cells resistant to ruxolitinib. Collectively, these findings identified BCL-XL as a key mediator of MPN-associated fibrosis and therapeutic resistance, and confirmed dual targeting of BCL-XL and JAK2 as a rational strategy for advanced MPN.

CONCLUSIONS Patients with PV treated with ruxolitinib can develop active tuberculosis, including disseminated forms. When tumor markers are elevated and imaging reveals lesions suggestive of metastases, clinicians should include disseminated tuberculosis in the differential diagnosis and pursue histopathological and microbiological investigations to enable timely diagnosis and appropriate treatment.

Emapalumab, alemtuzumab and ruxolitinib show promising results, however widespread use is limited by small, non-randomized trials in a heterogenous population. Further international collaborative efforts to develop clinical trials to put conventional chemotherapy treatments head-to-head with these newer therapies is critical for advancement of these agents.

Importantly, co-administration of ruxolitinib, a clinically approved JAK1/2 inhibitor, dampened IFN-β signaling and rescued mice from lethal toxicity. Collectively, these findings define the pathophysiological consequences of sustained systemic IFN-β exposure and identify ruxolitinib as a potential mitigation strategy to manage IFN-β-mediated toxicity during OV treatment.

P3, N=159, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=240 --> 159

P3, N=65, Recruiting, Alfasigma S.p.A. | Not yet recruiting --> Recruiting

While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders.

P1/2, N=112, Not yet recruiting, Shanghai Jiao Tong University School of Medicine

This study provides one of the first extensive characterizations of PV in southern Colombia, confirming internationally recognized clinical features, including advanced age at diagnosis, increased prevalence of cardiovascular comorbidities, and a predominance of high-risk classification. The low rate of finding JAK2 mutations suggests that molecular testing may not be as easy to get as it could be. Even if the treatment followed the guidelines, the risk of recurrence and thrombosis remained, showing that PV is a long-term and worsening condition. These findings highlight the urgent need to expand access to molecular diagnostics, develop tailored risk-adapted medicines, and initiate prospective multicenter studies in Latin America to optimize outcomes and quality of life in PV.

P=N/A, N=3000, Completed, Astellas Pharma Inc | Recruiting --> Completed

P1/2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P3, N=614, Active, not recruiting, AbbVie | Trial primary completion date: Sep 2025 --> Mar 2028