Even today, the diagnosis and therapeutic aspects of essential thrombocythemia (ET) still have many uncovered needs. With Protheragen's cutting-edge developments in diagnostics and therapeutics, we are ready to meet the challenges set by the management of ET. As a trusted partner in ET therapeutic research, we always provide comprehensive and high-quality services that fulfill your scientific research needs.
Essential thrombocythemia (ET) is a rare chronic blood disorder marked by excessive platelet production within the bone marrow. It is grouped within myeloproliferative disorders (MPN), a category of conditions defined by dysregulated blood cell production. In ET individuals, the raised platelet concentration increases the likelihood of thrombotic events or, put less frequently, hemorrhagic problems.
Fig. 1 Bleeding mechanisms in individuals with essential thrombocythemia (ET). (Awada, Hassan, et al., 2020)
The pathogenesis of essential thrombocythemia (ET) begins with genetic alterations, which leads to a cascade of signaling pathway dysregulation, cell pathological activities, and finally, culminates in excessive platelet production.
Genetic Mutations
ET is primarily caused by gene variants responsible for blood cell production. The most frequent alteration is the JAK2 V617F alteration which is present in 50-60% of the individuals with ET. Other significant mutated genes include CALR and MPL.
Dysregulation of Signaling Pathways
Key signaling pathways that promote excess proliferation and survival of megakaryocytes (the cells that produce platelets) are constitutively activated due to the genetic mutations. Among these, the JAK/STAT pathway is the most affected since it is constitutively activated by mutations of JAK2, CALR, or MPL.
Abnormal Megakaryocyte Behavior
Abnormal signaling pathways result in increased proliferation and survival of bone marrow megakaryocytes, which increases platelet production. Furthermore, changes in regulation of differentiation of megakaryocytes result in the generation of dysfunctional platelets.
By the year 2023, the myeloproliferative neoplasms (MPN) therapeutic market is anticipated to reach an estimated value between $6 to $8 billion, with essential thrombocythemia (ET) accounting for a significant proportion due to its prevalence among MPNs. The current treatment options consist of cytoreductive therapy, JAK inhibitors, and aspirin for symptom relief. However, there is considerable unmet need for new and better-targeted therapies. Focused development of new therapies is essential to improve therapeutic outcomes and constraints posed by current therapeutics.
Table. 1 Drug development pipeline for essential thrombocythemia (ET).
| Drugs | Types | Targeted Diseases | Developmental Stage |
|---|---|---|---|
| Ruxolitinib | JAK1/JAK2 inhibitor | JAK/STAT pathway | Approved |
| Fedratinib | JAK2 inhibitor | JAK2 | Approved |
| Pacritinib | JAK2/FLT3 inhibitor | JAK2, FLT3 | Approved |
| Interferon-alpha | Cytokine | Interferon signaling | Approved |
| Anagrelide | Thrombopoietin receptor agonist | MPL receptor | Approved |
| Hydroxyurea | Ribonucleotide reductase inhibitor | Ribonucleotide reductase | Approved |
| Bomedemstat | LSD1 inhibitor | LSD1 (epigenetic regulator) | Phase III |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our team at Protheragen strives to accelerate the battle with myeloproliferative disorders like essential thrombocythemia (ET) by providing full-scale diagnostic and therapeutic development services. We cover the entire spectrum in disease management, starting from developing in vitro diagnostic (IVD) kits to devising novel therapeutics. Incorporating advanced technologies and profound scientific understanding, we excel in developing precise disease models that intricately mimic the pathophysiology of ET.
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
Myeloproliferative Disorders (MPDs)
Bone Marrow Failure Syndromes (BMFS)
