A new study, co-led by Leukaemia UK and Wellcome funded researcher Dr Konstantinos Tzelepis at the Cambridge Stem Cell Institute, has uncovered a groundbreaking finding that could transform treatment for Acute Myeloid Leukaemia.
It has some of the worst survival rates of any cancer – nearly 80 per cent of people diagnosed with Acute Myeloid Leukaemia (AML) today will not survive beyond five years.
Dr Tzelepis (pictured), who was awarded a prestigious John Goldman Fellowship by Leukaemia UK in 2020, was part of a discovery that found a protein called Nucleophosmin (NPM1) – which was thought to only be present inside most normal cells – is also found on the surface of leukaemia cells.
This discovery challenges long-standing assumptions about cancer biology, and potentially opens up a whole new way to detect and target AML as well as other aggressive cancers with immunotherapy.
In immunotherapy, scientists look for proteins on the outside of cancer cells to help the immune system recognise and attack them, without harming healthy cells. While there are many immunotherapy treatments available, some subtypes of leukaemia do not respond to them. This research has identified a new protein target which could address this gap in treatment.
To test this idea Dr Tzelepis, with collaborators at the Boston Children’s Hospital and Harvard Dept. of Stem Cell and Regenerative Biology (US), led by Dr Ryan Flynn, developed a new antibody that targets NPM1 on the cell surface.
They studied its effects in laboratory models and patient samples, and found that the treatment successfully killed AML cells, prolonged survival, and restored healthy blood production — all without noticeable side effects.
Currently many treatments for AML attack both cancerous and healthy blood cells, meaning that there is a considerable level of drug toxicity and people diagnosed with AML are often left with life-long side effects after treatment.
One of the biggest challenges in treating AML is that many treatments only work for patients with certain genetic mutations, leaving many patients without any effective options. However, NPM1 levels are higher in cancer and its mutations are often found in AML, making it a treatment target that could help more patients.
Even more importantly, NPM1 is found in large amounts on leukaemia stem cells (LSCs) — the cells responsible for AML progression and relapse. Targeting these cells is currently difficult but could lead to treatments that not only get rid of leukaemia but also stop the disease from returning.
This collaborative study was co-first authored by Dr Benson George, of the Flynn Lab and Dr Maria Eleftheriou, a talented early career scientist who is currently funded by Dr Tzelepis’s John Goldman Fellowship Follow-up Fund award from Leukaemia UK.
If further pre-clinical and clinical studies confirm these findings, NPM1-targeted therapies could represent a major breakthrough for AML and potentially some other cancers e.g. prostate and colorectal cancers.
Dr Konstantinos Tzelepis said: “The development of novel cancer therapies is strongly dependent on biomedical research and the discovery of new cancer biology. I am very pleased that our collaborative work has led to a promising biotechnology approach to targeting cancers of unmet medical need, like AML. Our aim is to derisk and expedite the translation of these discoveries into new effective treatments.”
Fiona Hazell, CEO Leukaemia UK, said: “For the thousands of families in the UK devastated by AML each year, this is a vital breakthrough. Not only does it reshape our understanding of cancer biology, it opens the door to a new generation of immunotherapies that could deliver better outcomes for patients worldwide.
“We’re proud to support bold, innovative research led by early career scientists — work like this is essential if we are to achieve our goal of doubling the five-year survival rate for AML within the next decade.”
Dr Ryan Flynn said: “Our work highlights how the combination of basic and translational science can be effectively combined to advance new ideas.
“In the past, targets like NPM1 were disregarded because there was no logic for it to be a marker, but combining our mutual interests in RNA biology pushed us to do the work to that resulted in this exciting discovery.”
Dr Maria Eleftheriou said: “Current treatments for AML often come with severe side effects and don’t always provide a lasting solution. This exciting discovery is at an early stage, but has the potential to improve survival rates and quality of life for AML patients. As well as offering hope for developing similar targeted therapies for other cancers in the future.”
Dr Tzelepis and his group have made great strides in AML research in recent years, with some of their work already showing meaningful clinical outcomes. He is currently involved in the development of new therapeutic approaches that target AML and other cancers, which could lead to a new treatment that may give thousands of cancer patients a better chance of survival.
