Myeloproliferative Neoplasms (MPNs)

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the aberrant proliferation of one or more myeloid lineages. As a preclinical research service provider dedicated to oncology preclinical development, Alfa Cytology offers comprehensive, customized one-stop preclinical research services for MPNs. Leveraging deep expertise in cancer biology, state-of-the-art in vivo modeling platforms, and integrated diagnostic and therapeutic development capabilities, our company provides end-to-end solutions spanning target validation, efficacy evaluation, pharmacokinetic and pharmacodynamic profiling, and biomarker discovery.

Overview of Myeloproliferative Neoplasms (MPNs)

Characterized by the clonal proliferation of mature myeloid lineage cells within the bone marrow, Myeloproliferative Neoplasms (MPNs) comprise a heterogeneous group of chronic hematologic malignancies predominantly including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF). Driven by hematopoietic stem cell driver mutations that induce constitutive cytokine signaling, these diseases manifest through elevated peripheral blood counts, bone marrow hypercellularity, splenomegaly, an increased risk of thrombotic or hemorrhagic complications, and a propensity for leukemic transformation into acute myeloid leukemia (AML).

Fig.1 Association of mutational status with overall survival in MPNs. (Greenfield, G., et al., 2021)

Pathogenesis of Myeloproliferative Neoplasms (MPNs)

At the molecular core of classical MPN pathogenesis lies the dysregulation of the JAK-STAT signaling pathway, most frequently triggered by somatic gain-of-function mutations in the JAK2 (notably JAK2 V617F), CALR (calreticulin), and MPL (thrombopoietin receptor) genes. These driver alterations induce ligand-independent activation of downstream cytokine receptor signaling cascades, promoting uncontrolled hematopoietic cell proliferation and survival while altering the bone marrow microenvironment through inflammatory cytokine hypersecretion, ultimately culminating in progressive marrow fibrosis and extramedullary hematopoiesis.

Therapy Development for Myeloproliferative Neoplasms (MPNs)

Our Services

Leveraging comprehensive oncology research capabilities spanning molecular biology, in vivo pharmacology, histopathology, and bioanalytical sciences, Alfa Cytology provides tailored preclinical services across the full spectrum of MPN research and drug development.

Workflow for MPNs Preclinical Research

• Initial Consultation & Study Design: Aligning on strategic client objectives, evaluating target feasibility, defining genomic driver selection, and co-developing a customized preclinical study protocol tailored to specific experimental endpoints.
• Target Assessment & Assay Setup: Evaluating client-specified molecular pathways, characterizing drug target engagement mechanisms, and establishing custom biochemical, enzymatic, and baseline cell culture assays.
• In Vitro Efficacy Screening: Assessing anti-proliferative activity, apoptotic induction, downstream signaling inhibition, and colony-forming capacity using human MPN cell lines and primary hematopoietic stem/progenitor cells.
• Custom Animal Model Generation: Developing bespoke in vivo platforms, including conditional knock-in, cell line xenograft, or retroviral transplantation models, matching the specific genomic drivers of the target therapy.
• In Vivo Compound Evaluation: Executing systematic dosing studies in custom MPN models to determine optimal therapeutic windows, pharmacokinetics/pharmacodynamics profiles, and target tissue exposure.
• Phenotypic & Pathological Endpoint Analysis: Monitoring spleen weight reduction, peripheral blood cell counts, bone marrow megakaryocyte architecture, reticulin fibrosis progression, and inflammatory cytokine panels.
• Data Synthesis & Translational Reporting: Performing rigorous biostatistical calculations, multi-omics correlation, and integrated study documentation to support subsequent translational research decisions.

Comprehensive Preclinical Service for MPNs

Animal Model Development Service for MPNs

Tailored to the precise genomic driver mutations and microenvironmental complexities of hematologic malignancies, specialized custom animal model development services are provided to establish predictive in vivo platforms for MPN research.

Case Study-JAK2 V617F Knock‑in Mouse Model

To evaluate the pharmacodynamic profile of a candidate JAK inhibitor, Jak2-V617F knock-in mice were divided into treatment and vehicle control groups alongside age-matched wild-type controls. Animals received oral administration of either the test compound or vehicle over a multi-week dosing period, with baseline blood collected prior to initiation. Body weights and complete blood counts were routinely monitored at specified intervals throughout the study. Following treatment completion, animals were euthanized for harvest of spleens and bone marrow tissues to assess organ index and histological markers. Drug administration markedly attenuated elevated white blood cell counts in Jak2-V617F mice compared to vehicle-treated controls. Additionally, macroscopic examination revealed that targeted treatment effectively suppressed disease-associated splenomegaly, resulting in a significant decrease in spleen mass and index.

Fig.2 Pharmacodynamic evaluation of a targeted JAK inhibitor in the JAK2 V617F knock-in MPN mouse model. (A-C) Complete blood count parameters, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts across treatment groups. (D) Spleen index assessment following harvest at the study endpoint. Data are presented as mean ± SEM (n=6, ***p < 0.001, **p < 0.01).

Why Choose Us?

• Deep Expertise & Collaborative Design: Supported by experienced research scientists, hematopathologists, and bioinformaticians dedicated to co-designing tailored study protocols and providing scientific insights for research programs.
• Tailored Animal Model Engineering: Driven by advanced genetic engineering platforms to deliver bespoke model development services, including conditional transgenic, knock-in, and patient-derived xenograft strategies.
• End-to-End Solutions: Engineered to provide a preclinical workflow spanning target discovery, phenotypic diagnostic assay refinement, complex microenvironment modeling, and comprehensive candidate profiling, all within a single network.
• High-Quality Data & Rigorous Standards: Backed by strict quality-assurance frameworks, validated histopathological endpoints, and robust biostatistical reporting, delivering reproducible, high-integrity data aligned with research standards.

Contact Us

Myeloproliferative neoplasms present substantial unmet needs for disease‑modifying therapies beyond symptom management. Alfa Cytology is uniquely positioned to accelerate MPN therapeutic development through integrated, customized preclinical research services that combine scientific excellence, operational efficiency, and regulatory expertise. From genetically engineered mouse models to patient-derived systems, from target validation to IND-enabling studies, our company delivers the comprehensive support required to advance novel MPN therapeutics from concept to clinic. For more information about our MPN preclinical research capabilities or to discuss a specific project, please contact our scientific team.

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