“For the 60–70% patients who do not respond well to conventional chemotherapy, we hope by understanding their unique genetic underpinnings and specific responses to novel therapies, we may provide leads for clinical trials to evaluate their clinical efficacy.”
Each year the Research Grants Council, one of Hong Kong’s main research funding bodies, awards large research grants to projects of strategic importance to the long-term development of Hong Kong.
This year Professor Anskar Leung, Li Shu Fan Medical Foundation Professor in Haematology, of HKUMed successfully secured a $42 million HKD funding for his project “Towards Personalized and Innovative Treatment for Acute Myeloid Leukaemia” through the Theme-based Research Scheme in as part of the theme Promoting Good Health.
We spoke with Professor Leung about his project and what keeps him motivated in the fight against one of the most lethal cancers.
Congratulations on securing funding through the RGC Theme-based Research Scheme.
Your project “Towards Personalized and Innovative Treatment for Acute Myeloid Leukaemia”, can you tell us more about your project?
This project aims to study the effects of mutation combinations on blood formation with a view to determine their roles in the initiation of Acute Myeloid Leukaemia (AML), and their response to novel agents. This is accomplished by making use of zebrafish, a model that is uniquely suitable for this purpose.
In addition, our team has established an archive of more than 2000 blood and bone marrow samples from patients with AML that can be used to validate results from zebrafish with respect to specific mutation combination and their roles in AML formation and progression. These AML cells, with well-annotated genetic and clinical information, will become an invaluable source of materials in our AML research.
Furthermore, our team has initiated a few clinical trials at Queen Mary Hospital to test specific treatments for some of the most difficult-to-treat AML subtypes. Patient samples will be carefully collected during the course of treatment for genomic and biologic investigations so that the effects of these treatments can be enhanced and patient outcomes can be improved in the future.
For this study, you specified that the project would use the Zebrafish as the animal model, why is that? What makes them unique?
Interestingly, the zebrafish genome and the fundamental life processes in this organism are remarkably similar to those in humans.
The process and regulation of blood formation by Zebrafish (known as haematopoiesis) are remarkably similar to those in humans.
Zebrafish are also optically transparent, and their embryonic development is rapid. It takes less than 48 hours for a fertilised egg at one cell stage to grow into a larva with a functional circulatory system with visible blood cells under simple dissecting microscope.
Also, the genome of a Zebrafish is remarkably similar to that of humans and the embryos are highly amendable to genetic manipulation and pharmacological treatment.
Do you have any state-of-the-art technology planned for this project?
For this project, we plan on applying state-of-the-art technologies including genome editing, transgenesis, xenotransplantation, and genomic studies in single cells or in bulk.
The title of your projects mentions personalised treatment for AML, how does this relate to the different mutations in AML and how many mutations have been discovered so far?
With the advent of new sequencing technology in the past decade, new mutations of AML were identified at an unprecedented rate. At present, there are at least 30+ gene mutations frequently identified in AML and the number would likely increase.
On most occasions, these mutations occur in a duo or trio combinations, giving rise to hundreds of possibilities, hence the genetic and clinical diversities that are characteristics of this disease.
Hopefully, the zebrafish model with its high throughput will help us address the issue of genetic diversities of this disease.
How is this different from current treatment methods? What are the limitations?
Conventional treatment of a one-size-fits-all approach using chemotherapy is only effective for 30–40% of patients whose AML is chemo-sensitive. For the remaining majority of patients, there is an unmet clinical need to identify specific, or personalised treatment based on their unique gene mutation profiles. The present programme is designed to address the issues of genetic diversity in AML and the need for mutation-specific treatment with an aim to provide leads for evaluation in clinical trials
You mentioned to me that conventional methods are unable to treat the variety of mutations and the different combinations of AML, why is it still being used?
The reason perhaps is the lack of a robust platform with high throughput that can address the issue of diversities. That’s why we think our proposal comes in timely.
You’ve talked about how current conventional methods may fit about 30–40% of AML patients, how do you image a laboratory platform developed from your study can help the rest of the AML patients?
For the 60–70% patients who do not respond well to conventional chemotherapy, we hope by understanding their unique genetic underpinnings and specific responses to novel therapies, we may provide leads for clinical trials to evaluate their clinical efficacy.
And the 30% who respond to conventional methods, I assume they will also benefit from this study.
For the 30–40% patients who respond to conventional chemotherapy, results arising from the proposal will provide leads for testing chemo-free regimens that may reduce the toxicity of chemotherapy.
What do you think the public can expect to see from your project?
We expect information arising from his research will provide important leads for future clinical trials that may improve the treatment outcomes of patients whose outcome is hitherto dismal. The information will not only disseminate to the scientific communities but also to the general public to increase their awareness of this and related diseases and the relevance of scientific research to health care in Hong Kong.
So far, has your research findings been used in the treatment of patients?
Experiments based on genetic diversities of AML have resulted in the identification of a drug known as omacetaxine mepessucinate (formerly homoharringtonine) that was shown to be an effective adjunct in the treatment of a difficult-to-treat AML subtype carrying a mutation known as FLT3-ITD.
This drug is now widely used territory-wide for this AML subtype in Hong Kong. The lessons learnt from those studies have contributed significantly to the formulation of the project proposal.
One of the aims of your project is to establish Hong Kong as a leader in research and treatment for blood cancer, how does Hong Kong fit into your vision for this project?
Our track records in zebrafish leukaemia research and expertise in genome editing, our capture of precious patient samples that were well-annotated, our expertise in organising clinical trials, and the efficient health care system in Hong Kong have all placed Hong Kong in a unique position to become a regional hub for research and treatment for blood cancers.
Acute Myeloid Leukaemia is a lethal cancer is fighting it must be very tough mentally, what keeps you going despite facing such a devastating disease?
The daily encounters with blood cancer patients and their families at their moments of joy and grief have become my sources of motivation and challenges in our leukaemia research.
AML is a devastating disease for which treatment has been stagnant for a long time and yet scientific advancement has progressed rapidly in the past decade, clinicians and scientists in the leukaemia communities all feel obliged to contribute to the betterment of patient treatments.
Thank you for your time, Professor Leung. We look forward to seeing the impact your project will make.
Thank you for having me.