Myeloproliferative Neoplasm

P1, N=46, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2030 --> May 2028 | Trial primary completion date: Feb 2030 --> May 2028

P1, N=48, Recruiting, Sawa Ito, MD | Not yet recruiting --> Recruiting

We also devised a method to boost the cell surface expression of mutCALR in CD34+ cells isolated from patients with accelerated/blast phase MPNs (defined as >10% blasts in the peripheral blood or bone marrow), enhancing CAR T cell targeting. This study presents a therapeutic strategy with potential to eradicate mutCALR-driven malignancies and highlights an innovative strategy to evaluate blood cancer-targeting immunotherapies in a relevant TME.

The patient received therapeutic anticoagulation, low-dose aspirin, and hydroxyurea. This case highlights the role of multimodal imaging in diagnosis and risk stratification, and the need to consider masked polycythemia vera in unprovoked pulmonary embolism with unexplained microcytosis and elevated red blood cell count.

P1, N=20, Not yet recruiting, Roswell Park Cancer Institute

P2, N=49, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027

In this evidence-based review, we trace the evolution of risk stratification in PV and ET and examine the clinical evidence supporting current cytoreductive options, specifically hydroxyurea, interferons, ruxolitinib, and anagrelide. We argue for a paradigm shift away from binarily driven thrombosis-centric risk stratification toward a personalized, proactive approach that integrates molecular and inflammatory biomarkers, expands the population offered cytoreduction, and prioritizes disease-modifying therapies. Prospective studies are needed to validate the incorporation of these markers into risk-adapted algorithms and to define the long-term impact of early disease modification on transformation, survival, and quality of life.

Together, these approaches support a new ecological model of MPN pathogenesis in which early epigenetic hits create permissive stem cell reservoirs, clonal competition and cooperation shape disease progression, and non-cell-autonomous niche and immune signals drive malignant metamorphosis. We discuss how this framework refines prognostication, informs rational combination therapies targeting both malignant cells and their ecosystem, and enables real-time monitoring of clonal dynamics, ultimately charting a course from descriptive atlases to actionable clinical strategies.

Acetylsalicylic acid (ASA) decreased the abundance of metabolic proteins in CALR Type1 platelets, whereas JAK2 V617F platelets showed only minor, heterogeneous increases restricted to a subset of proteins and samples. In functional assays, JAK2 V617F platelets showed aggregation responses similar to or lower than those of healthy controls, whereas untreated CALR Type2 platelets showed higher CD62P expression, indicating a more activated phenotype than the other ET groups. These findings indicate that ET platelets display mutation-associated proteomic and functional differences and suggest that an altered metabolic state may contribute to platelet reactivity.

The patient was treated with cladribine (40 mg over five days) followed by maintenance hydroxyurea (300 mg twice daily), with significant clinical improvement at eight-week follow-up. This case underscores that SM-AHN can present with isolated hepatosplenomegaly and profound leukocytosis without cutaneous signs, and highlights the critical role of integrated molecular profiling, including KIT mutation analysis, in the diagnostic workup of atypical hematologic presentations.

We describe a 74-year-old woman with JAK2V617F-mutated myeloproliferative neoplasm and hydroxyurea intolerance who presented with active mucosal bleeding and a platelet count of 952 000/μL...Repeat testing at 24 h showed improvement in vWF:RCo to 0.48 IU/mL (ratio 0.68), which likely reflects restoration of functional high-molecular-weight multimers. In this single case, thrombocytapheresis provided rapid and effective platelet reduction for AvWD secondary to myeloproliferative neoplasms when pharmacological cytoreduction is inadequate.

Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.