Customized Solutions for Myeloproliferative Neoplasms (MPNs) Model Development

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Characterized by the clonal proliferation of mature myeloid lineages, myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), present distinct therapeutic challenges driven by specific somatic mutations such as JAK2 V617F, CALR, and MPL.

Bridging the gap between mechanistic discovery and clinical translation, Protheragen provides end-to-end preclinical solutions tailored to novel MPN drug discovery. By offering fully customized MPN Model Development alongside an integrated suite of downstream evaluation services, research programs receive comprehensive support from early target validation to IND-enabling preclinical studies.

Overview of Myeloproliferative Neoplasm (MPN) Models

Recapitulating the complex pathophysiological hallmarks of human MPNs, such as persistent JAK-STAT pathway activation, bone marrow hypercellularity, splenomegaly, and progressive reticulin fibrosis, demands advanced, high-fidelity disease models. Utilizing genetically engineered mouse models (GEMMs), patient-derived xenografts (PDX), and knock-in/transgenic approaches, modern MPN models replicate driver-mutation biology (JAK2, CALR, MPL) and secondary clonal evolution. These platforms serve as vital testbeds for evaluating molecular targets, deciphering microenvironmental crosstalk within the hematopoietic niche, and assessing therapeutic interventions designed to alter disease burden or prevent leukemic transformation.

Applications of MPN Animal Models

Enabling comprehensive exploration of clonal myeloproliferation, tailored MPN models provide indispensable tools for functional genomics, translational pharmacology, and biomarker discovery.

Workflow for MPN Animal Model Development and Research

• Project Scoping and Model Selection: Collaborative consultation to define study objectives, select the appropriate MPN model (genetically engineered, transplantation-based, or xenograft), and establish critical success criteria based on the specific MPN subtype and therapeutic modality of interest.
• Model Generation and Characterization: Generation of MPN models via bone marrow transplantation of mutant hematopoietic cells, gene editing, or transgenic approaches, followed by comprehensive baseline characterization including complete blood counts, splenomegaly assessment, bone marrow histology, and flow cytometric immunophenotyping.
• Disease Establishment: Monitoring of disease engraftment and progression through serial hematologic analysis and, where applicable, in vivo imaging, ensuring that therapeutic intervention occurs at the appropriate disease stage.
• Therapeutic Intervention and Dosing: Administration of test compounds via optimized dosing regimens (oral, intravenous, intraperitoneal), with pharmacokinetic sampling to establish exposure-response relationships.
• Efficacy and Pharmacodynamic Assessment: Comprehensive evaluation of therapeutic activity, including peripheral blood counts, spleen weight and histopathology, bone marrow fibrosis scoring, flow cytometric analysis of hematopoietic progenitor compartments, and molecular analyses of target engagement and pathway modulation.
• Toxicological and Safety Profiling: Integrated assessment of tolerability, body weight changes, clinical chemistry, and histopathological evaluation of major organs to support IND-enabling studies.
• Data Analysis and Reporting: Rigorous statistical analysis, preparation of detailed study reports, and delivery of actionable insights to guide lead optimization and candidate selection.

Available MPN Animal Models

Integrated Preclinical Research Services for MPN

Beyond model development, our company delivers a fully integrated suite of preclinical research services designed to support MPN drug development from early discovery through IND-enabling studies.

Case Study -JAK2 V617F Knock-in Mouse Model

For this pharmacodynamic assessment, JAK2 V617F knock-in mice on the C57BL/6 background were selected as the disease model, with age-matched wild-type littermates serving as normal reference controls. Throughout the 41-day therapy phase, daily oral administration of the drug or vehicle was performed, while body weight measurements and blood sampling were carried out at baseline (Day 0) and at regular intervals across the dosing period, culminating in terminal tissue collection on Day 42.

Fig.1 Peripheral white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts obtained via complete blood count (CBC) analysis. Elevated levels of all three parameters were evident in JAK2 V617F mice relative to wild-type controls, consistent with the MPN disease phenotype. A significant decline in WBC counts was observed in mice receiving the drug compared to vehicle-treated counterparts. Data are presented as mean ± SEM (n=6; ***p < 0.001, **p < 0.01).

Marked reductions in peripheral white blood cell counts were observed in the drug-treated cohort relative to the vehicle-treated group, whereas red blood cell and platelet parameters remained largely unaltered across the disease groups. Concomitantly, a substantial decrease in spleen size was documented, with the calculated spleen index (spleen weight normalized to body weight) showing significant improvement following drug intervention, an outcome attributable to the attenuation of extramedullary hematopoiesis, a hallmark feature of MPN-associated splenomegaly.

Fig.2 Amelioration of disease-associated splenomegaly, expressed as the spleen index calculated at study termination (Day 42). A notable reduction in the spleen index was achieved in the drug-treated group compared to the vehicle control group, reflecting the alleviation of extramedullary hematopoiesis and confirming the therapeutic impact on a key pathological feature of MPNs. Data are presented as mean ± SEM (n=6; ***p < 0.001).

Why Choose Us?

• MPN-Specialized Expertise: Specialized expertise in MPN biology and preclinical modeling, with an experienced team to ensure biologically informed and clinically relevant study designs.
• Broad Selection of Models: Customized model development services tailored to specific research needs, offering flexible solutions across various MPN subtypes and disease stages.
• Integrated Service Platform: Integrated service platform covering model development, efficacy testing, and toxicology within one organization, streamlining workflows and ensuring consistent data quality.
• Translational and Regulatory Focus: Rigorous scientific approaches with comprehensive data reporting to support clear decision-making and accelerate program advancement.

Contact Us

Protheragen’s comprehensive MPN model development and integrated preclinical research services provide a robust, end-to-end platform for advancing MPN therapeutics from discovery to the clinic. With MPN-specialized expertise, a diverse model portfolio, and a translational focus, our company is uniquely positioned to support pharmaceutical and biotechnology partners in their efforts to develop disease-modifying therapies. To discuss how our MPN capabilities can accelerate your program, please contact us.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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