12 Nov Duke-NUS Finds Genetic Variant in East Asians Makes CML Harder to Treat
MedicalResearch.com Interview with:
Prof. Ong Sin Tiong
Professor Ong Sin Tiong
Cancer & Stem Cell Biology Signature Research Programme
Duke-NUS Medical School, Singapore
Dr. Yu Mengge
Dr Yu Mengge
Research Fellow, Cancer & Stem Cell Biology Signature Research Programme
Duke-NUS Medical School
MedicalResearch.com: What is the background for this study?
Response: The background of this study is rooted in the observation that certain genetic variations among East Asian populations, notably the BIM deletion polymorphism (BDP), impact treatment outcomes in chronic myeloid leukaemia (CML).
Patients with the BDP show resistance to conventional treatments, specifically tyrosine kinase inhibitors like imatinib. This resistance stems from the variant’s role in promoting cancer cell survival, which leads to more aggressive disease progression.
MedicalResearch.com: What are the main findings?
Response: Our main findings reveal that leukaemia cells carrying the BDP promote a more aggressive form of the disease. These specific stem cells rely heavily on a protein called MCL-1 for survival, making MCL-1 a promising target for overcoming drug resistance in these cases. By inhibiting MCL-1, we were able to significantly impact the survival of these aggressive leukaemia cells, suggesting a new approach for treating patients with this genetic variant.
MedicalResearch.com: What should readers take away from your report?
Response: The key takeaway is that genetic variations we inherit from our parents, like the BDP, can significantly impact how we respond to standard cancer treatments.
Our findings highlight the potential of genetic profiling in CML, which could help clinicians identify patients who may not respond to first-line therapies alone and may benefit from alternative or combination treatments early in their diagnosis.
For those with the BDP, combining MCL-1 inhibition with traditional therapies offers a more targeted and potentially more effective approach.
It will be important for future research to highlight other inherited variations that affect how Asians with cancer respond differently to each other, as well as to non-Asian individuals.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Future research could also explore the impact of the BDP in other diseases beyond leukaemia, such as certain types of lung cancer.
Additionally, larger clinical studies are essential to validate our findings and understand the long-term effects of combining MCL-1 inhibitors with existing treatments.
Lastly, integrating genetic screening into routine clinical practice could refine treatment plans and enhance outcomes for patients with specific genetic profiles.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: We’d like to emphasise the collaborative nature of this study. We worked closely with Singapore General Hospital and The Jackson Laboratory, leveraging each institution’s strengths in both clinical insights and advanced laboratory modelling. This collaboration has been key in translating our findings into meaningful implications for patient care.
Citation:
Yu, M., Nah, G.S.S., Krishnan, V. et al. The BIM deletion polymorphism potentiates the survival of leukemia stem and progenitor cells and impairs response to targeted therapies. Leukemia (2024). https://doi.org/10.1038/s41375-024-02418-0
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Last Updated on November 13, 2024 by Marie Benz MD FAAD