Acute Megakaryoblastic Leukemia (AMKL)
Acute megakaryoblastic leukemia (AMKL) is an intriguing and intricate ailment. However, a glimmer of hope is on the horizon as breakthroughs in targeted therapy development illuminate the path towards effective AMKL therapies. Within the realm of innovation and advancement lies our company, resolute in its mission to push the boundaries of AMKL drug and therapy development.
Overview of Acute Megakaryoblastic Leukemia (AMKL)
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal proliferation and maturation of megakaryocytes, the cells responsible for platelet production. AMKL accounts for approximately 5% of pediatric AML cases and 2-3% of adult AML cases. It is particularly prevalent in individuals with Down syndrome (DS-AMKL), where it represents up to 20% of AML cases.
- Pathogenesis of AMKL
The pathogenesis of AMKL involves genetic alterations that disrupt normal megakaryocyte development and function. In DS-AMKL, the most common genetic abnormality is the GATA1 mutation, leading to the production of a truncated GATA1 protein. This mutation is crucial for leukemogenesis and is considered a hallmark of DS-AMKL. Non-DS-AMKL, on the other hand, is characterized by various chromosomal translocations, such as CBFA2T3-GLIS2 and KDM1A rearrangements.
Fig.1 Genetic events in Down syndrome (DS)-AMKL. (McNulty M., and Crispino J. D., 2020)Targets of Acute Megakaryoblastic Leukemia (AMKL)
- GATA1
For DS-AMKL, targeting the GATA1 mutation and its downstream pathways is paramount. A study demonstrated that inhibition of GATA1 expression using small interfering RNA (siRNA) resulted in decreased proliferation and increased apoptosis in DS-AMKL cell lines. This finding highlights the potential of targeting GATA1 as a therapeutic strategy.
- CBFA2T3-GLIS2
In non-DS-AMKL, various chromosomal translocations provide potential targets for therapy development. The CBFA2T3-GLIS2 fusion protein, commonly found in non-DS-AMKL, has been identified as a key player in leukemogenesis. A study showed that interfering with the CBFA2T3-GLIS2 fusion protein using short hairpin RNA (shRNA) inhibited leukemic cell proliferation and induced megakaryocytic differentiation. This finding suggests that targeting CBFA2T3-GLIS2 could be a therapeutic approach for non-DS-AMKL.
- KDM1A
The KDM1A protein has been implicated in non-DS-AMKL translocations. Inhibition of KDM1A has shown promising anti-leukemic effects. A study demonstrated that therapy with a selective KDM1A inhibitor, GSK2879552, resulted in decreased cell viability and induction of differentiation in non-DS-AMKL cell lines. This study provides evidence for the therapeutic potential of targeting KDM1A in non-DS-AMKL.
Our Services
By choosing our company for AMKL diagnostics and therapy development services, clients can expect exceptional expertise, customized solutions, and a commitment to advancing the field of AMKL research and drug development. Our company prioritizes, data integrity, and confidentiality, ensuring that our services are conducted with the utmost integrity and professionalism.
Our AMKL Therapy Development Platforms
Developing effective therapies for AMKL relies on robust preclinical animal models that accurately mimic the disease. Our company has established the most advanced AMKL animal model, which can conduct in-depth research, including pharmacokinetics studies and drug safety evaluation, to accelerate AMKL drug development.
Animal models of AMKL
- AML Zebrafish models
- Chemically-induced models (3-methylcholantrene)
- Radiation-induced model
- Virally-induced leukemia models
- Single mutation models
- Compound transgenic mouse models
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- McNulty M., and Crispino J. D. "Acute megakaryocytic leukemia." Cold Spring Harbor Perspectives in Medicine 10.2 (2020).
- De Marchi, Federico, Marito Araki, and Norio Komatsu. "Molecular features, prognosis, and novel treatment options for pediatric acute megakaryoblastic leukemia." Expert Review of Hematology 12.5 (2019): 285-293.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.