Chronic myelomonocytic leukemia (CMML) has features of both myelomonocytic disorders and myeloproliferative disorders (MDS/MPN) which complicates its diagnosis and treatment. Thanks to our extensive knowledge in CMML therapy development, Protheragen is uniquely equipped to offer customized solutions and strategic support in your transition from CMML therapy research towards commercialization.
Chronic myelomonocytic leukemia (CMML) is a rare complex blood malignancy classified as myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). It is marked by the excessive generation of defective monocytes (a class of white blood cells) within the bone marrow. As a result, monocytes overflow into the blood and extramedullary tissues. This makes normal blood cell production difficult, and the patient may experience fatigue, infections, anemia, and an enlarged spleen.
| Disease Subtypes | Features | Incidence |
|---|---|---|
| CMML-1 | Blasts account for less than 5% in the blood and less than 10% in the bone marrow. | 60–70% |
| CMML-2 | Blasts account for 5–19% in the blood or 10–19% in the bone marrow. | 30–40% |
The origin of chronic myelomonocytic leukemia (CMML) has its roots in an amalgamation of genetic mutations, signal dysregulation on the pathway, in addition to epigenetic abnormalities. Mutations within the critical TET2, ASXL1, SRSF2, and RAS genes are known to produce cells which don't fully differentiate and promote the monocytic cellular clonality expansion. Other significant alterations like excessive methylation of DNA sequences modify gene expression while overactivation of signaling pathways such as JAK-STAT and RAS-MAPK are capable of uncontrolled hyperproliferative cellular activity.
Fig. 1 Oncogene families in chronic myelomonocytic leukemia (CMML). (Itzykson, Raphael, et al., 2017)
At present, therapeutic options for chronic myelomonocytic leukemia (CMML) are scarce, leaving a significant number of unmet medical needs. The diverse genetic mutations and presentations associated with CMML, alongside the resistance of many affected individuals to current therapies, present numerous challenges to effectively treating this condition. Consequently, there is a pressing demand for the development of novel therapies to better address the management of CMML.
Table. 1 Therapy development pipeline for chronic myelomonocytic leukemia (CMML).
| Drugs | Types | Targets | Development Stage |
|---|---|---|---|
| Decitabine | Hypomethylating agent | DNA methylation | Approved |
| Venetoclax | BCL-2 inhibitor | BCL-2 protein | Approved |
| Ruxolitinib | JAK1/JAK2 inhibitor | JAK-STAT pathway | Approved |
| Pevonedistat | NEDD8-activating enzyme inhibitor | Protein degradation pathways | Phase III |
| Imetelstat | Telomerase inhibitor | Telomerase activity | Approved |
| Tagraxofusp | CD123-targeted therapy | CD123 (IL-3 receptor) | Approved |
| IDH1/2 Inhibitors | Mutant IDH1/2 inhibitors | IDH1/2 mutations | Approved |
| TP-3654 | PIM kinase inhibitor | PIM kinases | 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.
Recognizing the complexity of diagnosing and treating chronic myelomonocytic leukemia (CMML), Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of CMML. These models are valuable tools for validating the safety and efficacy of potential therapeutics.
To accelerate preclinical research and therapeutic development for rare and complex diseases, including chronic myelomonocytic leukemia (CMML), our company specializes in developing advanced animal models that replicate the genetic, molecular, and clinical features of human disease. Our models mainly include genetically engineered models, xenograft models, retroviral/BMT models, etc.
Optional Species: Mice, Rats, Zebrafish, Non-Human Primates, Others.
At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for chronic myelomonocytic leukemia (CMML). 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)