Advantages
- First detection method to detect minimal residual disease (MRD) in CEBPA-AML, which is in high demand for clinical testing.
- Highly sensitive detection: Detectable even when the percentage of mutated cells is very small.
Technology Overview & Background
Acute myelogenous leukemia (AML) is a group of diseases that can be subdivided into nearly 20 subtypes, with risk stratification based on genetic background, and HSCT (hematopoietic stem cell transplant) in the first remission stage is recommended for the intermediate- to high-risk group, while chemotherapy alone is recommended for the low-risk group. However, there are cases of relapse even in the low-risk group, which has a good prognosis. In particular, minimal residual disease (MRD) is considered an independent risk indicator for relapse, and its detection is a reason to choose transplantation in the first remission period. Therefore, detection of MRD during treatment and prognostic follow-up, especially in low-risk groups, is very important.
Currently, four types of AML in the low-risk group are known, and among them, AML with Inv(16) translocation, AML with t(8;21) translocation, and AML with NMP1 mutation all have established PCR-based MRD detection methods. On the other hand, for AML with CEBPA mutations, MRD detection methods have not been established because the mutation site varies from case to case, and the emergence of clinically reliable MRD testing methods is needed.
Therefore, the researchers devised a new method to easily detect mutations in the CEBPA gene, which corresponds to MRD, using next-generation sequencers (NGS) analysis. The CEBPA gene is a sequence rich in GC repeats, making it unsuitable for NGS analysis in the past. However, the inventor has established testing conditions and evaluation methods that are almost error-free in PCR and sequencing. As a result, the presence or absence of residual CEBPA gene mutations that patients had at the time of disease onset can be evaluated with high specificity and can be detected with high sensitivity (detectable at the 0.01% level). Hence, it is expected that this invention will be the most reliable MRD testing method for AML with CEBPA mutations.
Publication(s)
Currently in the pre-publication stage.
Patent(s)
A PCT application will be applied in 2024.
Researchers & Academic Institution
Jun Nakata, MD, PhD (Assistant Professor, Osaka University, Japan),
Haruo Sugiyama, MD, PhD (Professor, Osaka University, Japan),
Daisuke Motooka, PhD (Associate Professor, Osaka University, Japan), et al.
Development Stage & Future Research Plans
- In a retrospective observational study at Osaka University, the researchers confirmed that the MRD method was detectable in 31 AML cases with CEBPA mutations at the initial diagnosis.
- In addition, a significant difference in relapse rate (P<0.01) was observed between MRD-positive and MRD-negative cases after treatment with the invention in 20 patients who had completed chemotherapy.
- The researchers are now aiming for insurance coverage through a larger prospective study.
Expectations
TECH MANAGE is looking for companies that are interested in licensing this invention for commercialization as a test kit or as a contract analysis service. Under the confidentiality agreement (CDA) with Osaka University, we can disclose detailed information about the invention/project and hold meetings directly with the researchers, so please feel free to contact us if you have any requests.
Project.JT-04604