There is a remarkable opportunity in developing effective therapies for chronic neutrophilic leukemia (CNL). Taking advantage of our pioneering work in CNL research, Protheragen is currently developing advanced therapies that aim to improve the management of CNL. As your partner in CNL drug development research, we extend unrivaled assistance that fulfills your research requirements.
Chronic neutrophilic leukemia (CNL) is a highly aggressive, scarce form of blood cancer that occurs due to the overproduction of mature neutrophils in the bone marrow. These neutrophils are in excess and sequentially accumulate in the bloodstream. Later they invade different organs which can lead to plethora of complications. The overall occurrence of CNL annually is estimated at around one case per every million individuals, with a minor dominance in males.
Fig. 1 Proposed models of clonal evolution in chronic neutrophilic leukemia (CNL). (Thomopoulos, Thomas P., et al., 2022)
The development of chronic neutrophilic leukemia (CNL) involves multiple molecules and genetic factors, all of which lead to the overproduction and accumulation of mature neutrophils in the bone marrow and blood. Research has not pinpointed the exact cause for CNL, yet it has made considerable headway towards determining significant genetic mutations and signaling pathways fundamental to the condition's pathology.
Key Genetic Mutations in CNL
The colony stimulating factor 3 receptor (CSF3R) gene is the most commonly mutated gene in CNL, present in approximately 80-90% of cases. Mutations in CSF3R often result in constitutive activation of the receptor and downstream signaling pathways. Other mutated genes include SETBP1, ASXL1, TET2, SRSF2, and JAK2.
Dysregulated Signaling Pathways
CSF3R mutations usually activate JAK/STAT, RAS/MAPK and other signaling pathways. Dysregulation of the JAK/STAT pathway leads to uncontrolled cell proliferation and neutrophil survival. Activation of the RAS/MAPK pathway leads to abnormal cell growth and differentiation, further leading to overproduction of neutrophils.
Considering the aggressive character and the possibility of quick transformation into acute leukemia, chronic neutrophilic leukemia (CNL) requires proactively managed therapies. Currently, there are many approved and investigational CNL therapies with broad potential.
| Drugs | Types | Targeted | Developmental Stage |
|---|---|---|---|
| Ruxolitinib | JAK1/JAK2 inhibitor | JAK/STAT pathway | Approved |
| Momelotinib | JAK1/JAK2 inhibitor | JAK/STAT pathway | Approved |
| Pacritinib | JAK2/FLT3 inhibitor | JAK2, FLT3 | Approved |
| Trametinib | MEK inhibitor | RAS/MAPK pathway | Approved |
| Midostaurin | Multi-kinase inhibitor (FLT3, PKC, KIT) | FLT3, CSF3R | Approved |
| Venetoclax | BCL-2 inhibitor | BCL-2 | Approved |
| Selinexor | XPO1 inhibitor | XPO1 | Approved |
| CSF3R-Targeted Therapies | Monoclonal antibodies or small molecules | CSF3R | Phase I/II |
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.
Protheragen provides a full set of diagnostic and therapeutic development service to advance the effective management of chronic neutrophilic leukemia (CNL) using its vast expertise and modern technologies. We are committed to addressing the huge uncovered medical needs through innovative therapeutics that target the various driving molecular mechanisms of CNL. Our experts excel in developing highly accurate disease models which permit the comprehensive assessment of the safety, efficacy, and mechanism of action of new potential therapeutics.
The construction of a dependable animal model for chronic neutrophilic leukemia (CNL) is crucial for medical research. This model helps in the understanding of the disease's pathogenesis and progression while offering a platform for testing new therapies.
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| Genetically Engineered Models |
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| Induced Disease Models |
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| Xenograft Models |
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With high-quality animal models, Protheragen is committed to providing comprehensive preclinical research services covering pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies to support the development and regulatory approval of potential therapies for chronic neutrophilic leukemia (CNL). 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)