Chronic Myelomonocytic Leukemia (CMML)
Chronic myelomonocytic leukemia (CMML) is a rare hematological disorder characterized by the proliferation of abnormal cells in the bone marrow. It is a myelodysplastic/myeloproliferative neoplasm that shares features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). CMML is often challenging to diagnose and treat due to its complex nature and heterogeneity. Our company is at the forefront of drug and therapy development services for CMML, aiming to provide innovative solutions to combat this disease.
Overview of CMML
- Definition of CMML
CMML is rare, affecting approximately 4 individuals per 1 million individuals annually in the United States. CMML is a clonal disorder of hematopoietic stem cells that leads to the overproduction of monocytes and myeloid cells. It is primarily characterized by persistent monocytosis, dysplastic changes in the bone marrow, and an increased risk of transformation to acute myeloid leukemia (AML). CMML predominantly affects elderly individuals, with a median age at diagnosis of around 70 years. - Pathogenesis of CMML
The pathogenesis of CMML is multifactorial. Genetic mutations, such as those affecting genes involved in DNA methylation (TET2, DNMT3A), splicing machinery (SRSF2, SF3B1), and signaling pathways (RAS, JAK2), play a crucial role in the development and progression of CMML.
Diagnostics Development of CMML
- Genetic Testing
The common CMML-related mutations, including TET2, DNMT3A, SRSF2, SF3B1, and others, were analyzed by a gene testing panel. These tests aid in the identification of specific genetic abnormalities and assist in risk stratification and therapy decision-making.
- Flow Cytometry Assays
Flow cytometry is a valuable tool for assessing aberrant antigen expression patterns on hematopoietic cells. Flow cytometry assays can detect and quantify abnormal cell populations, including monocytic and myeloid cells, aiding in the diagnosis and monitoring of CMML.
Fig.1 Clonal evolutionary dynamics in patients with CMML. (Patnaik, Mrinal M., 2022)Therapy Development of CMML
- Differentiated Therapies
CMML-1 and CMML-2 are subtypes distinguished by the percentage of blasts in the bone marrow and peripheral blood. CMML-1 has less than 5% blasts, while CMML-2 has 5-19%. Targeted therapies for CMML-1 aim to control abnormal cell proliferation and promote differentiation, while therapies for CMML-2 focus on reducing blasts and preventing progression to acute myeloid leukemia (AML).
- Mutation-Specific Therapies
Specific genetic mutations, such as those affecting genes like TET2, DNMT3A, and SRSF2, can influence pathogenesis and prognosis of CMML. There is much interest in developing mutation-specific therapies that target the underlying molecular alterations associated with these mutations.
Our Services
By focusing on the pathogenesis, diagnostics, therapeutic targets, and subtypes of CMML, we are dedicated to developing personalized and effective therapies. Our company offers a range of services to support CMML therapy development and preclinical research. By combining scientific expertise and cutting-edge technologies, we strive to make a significant impact in the field of CMML therapy development.
Platforms of CMML Therapy Development
We conduct pharmacokinetic analysis to determine the absorption, distribution, metabolism, and excretion of drug candidates in CMML animal models. These studies provide valuable insights into the pharmacokinetic profile and dosage optimization of potential therapeutics. In addition, comprehensive drug safety evaluations are performed to ensure that potential therapies meet safety standards and mitigate risks.
CMML Animal Model Development Service
- CM-CSF downstream signaling pathway activation
- Epigenetic regulator mutation models
- Cell death control (BID) modified models
- Patient derived xenograft (PDX) models
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Patnaik, Mrinal M. "How I diagnose and treat chronic myelomonocytic leukemia." Haematologica 107.7 (2022): 1503.
- Kwon, Jihyun. "Diagnosis and treatment of chronic myelomonocytic leukemia." Blood research 56.S1 (2021): 5-16.
- Patnaik, Mrinal M., and Ayalew Tefferi. "Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management." American journal of hematology 95.1 (2020): 97-115.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.