Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a complex and aggressive form of leukemia that originates in the bone marrow, leading to the rapid proliferation of immature myeloid cells. As an experienced drug and therapy development service provider, we tailor solutions specifically for AML, and we are unwaveringly committed to in-depth research on the pathogenesis of AML and the development of therapies.
What is Acute Myeloid Leukemia (AML)?
Acute myeloid leukemia (AML), a remarkably intricate and relentlessly aggressive hematological malignancy, manifests its origins within the bone marrow, inciting a frenzied surge in the unchecked proliferation of immature myeloid cells. This tumultuous cellular expansion culminates in the perilous accumulation of aberrant myeloblasts, effectively throwing the delicate balance of blood cell production into disarray. AML is indeed a relatively rare form of cancer, accounting for approximately 1.1% of all cancer cases in the United States. Unfortunately, it also contributes to about 1.9% of cancer-related deaths in the country.
Pathogenesis of Acute Myeloid Leukemia (AML)
The pathogenesis of AML involves a series of genetic and epigenetic alterations that result in the abnormal proliferation and survival of myeloid progenitor cells. Several genetic mutations have been identified in AML, including mutations in genes such as FLT3, NPM1, and DNMT3A. These mutations can disrupt normal cellular processes, including cell signaling, transcriptional regulation, and DNA methylation, leading to uncontrolled cell growth and impaired differentiation.
Fig.1 History of AML therapies. (Carter J. L., et al., 2020)Targeted Therapy Development for AML
- BCL-2 Targeted Therapy
The BCL-2 family of proteins plays a crucial role in regulating apoptosis. Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in AML cells, contributing to their survival and resistance to therapy. Inhibitors targeting BCL-2 have demonstrated promising results in inducing apoptosis and enhancing the efficacy of standard chemotherapy regimens. - FLT3 Targeted Therapy
About 1/3 of AML is caused by mutations in the FLT3 gene. Inhibitors targeting the FLT3 receptor tyrosine kinase have shown promise in preclinical studies by inhibiting cell proliferation and promoting apoptosis in AML cells. These inhibitors achieve therapeutic goals by blocking abnormal FLT3 signaling.
- IDH Targeted Therapy
Some AML are caused by mutations in the isocitrate dehydrogenase (IDH) gene, especially IDH1 and IDH2. These mutations result in the accumulation of an oncometabolite, which interferes with normal cell differentiation. IDH inhibitors have been developed to target these mutant enzymes, reducing the levels of the oncometabolite and restoring normal differentiation. - Hypomethylating Agent Therapy
Aberrant DNA methylation patterns are a hallmark of AML. Hypomethylating agents are used to restore normal DNA methylation patterns, leading to reactivation of tumor suppressor genes and inhibition of leukemic cell growth.
Our Services
Utilizing cutting-edge technologies and expertise, we identify and validate potential therapeutic targets in AML. Through in-depth analysis of genomic and molecular data, we prioritize targets with high therapeutic potential. Our experienced team of scientists utilizes state-of-the-art techniques in diagnostics and drug development to create novel therapeutics for AML.
Our AML therapy development platforms:
We conduct rigorous preclinical testing and evaluation of potential AML therapeutics using relevant animal models, including xenograft and GEMM models. This enables a comprehensive assessment of efficacy, pharmacokinetics, and safety profiles to inform further development.
Optional animal model development services include but are not limited to
- Xenograft models were constructed using patient-derived AML cells.
- PDX models were constructed using patient-derived AML samples.
- FLT3-ITD mutation models were constructed by genetic engineering technology.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Carter J. L., et al. "Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy." Signal Transduction and Targeted Therapy 5.1 (2020): 288.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.