Could blocking an enzyme be the missing piece to transform AML treatment?

By developing and characterising a small molecule which blocks the action of METTL1, Dr Yankova aims to create a new treatment that slows leukaemia growth.

Dr Eliza Yankova from the University of Cambridge focuses on developing innovative treatments for Acute Myeloid Leukaemia (AML). Her research targets the enzyme METTL1, which plays a key role in AML development. By developing and characterising a small molecule which blocks the action of METTL1, Dr Yankova and collaborators aim to create a highly specific treatment that slows leukaemia growth while sparing healthy cells.

The Challenge:
Acute myeloid leukaemia (AML) is a fast-growing and aggressive blood cancer that affects both young and older adults, with outcomes varying significantly by age. Younger patients under 40 have a five-year survival rate of around 55%, while older patients face much poorer odds, with survival dropping to around 20%.[1] Although recent advances in combination therapies have offered some temporary relief, these treatments often come with severe side effects and don’t always provide a lasting solution. There is a critical need for new treatments that specifically target the cancer while minimising side effects, making the recovery process less dangerous and more manageable for patients.

The Research:
This study is focused on RNA – or ribonucleic acid, is a molecule that carries instructions from DNA to make proteins – modifications in AML, particularly the role of a key enzyme known as METTL1, which creates a chemical marker (m7G) on the tRNA molecules.[2] These modifications help cancer cells thrive, and METTL1 has been found to be overactive in AML. This drives the cancer’s progression. Researchers are developing a first-in-class small-molecule inhibitor to block METTL1’s activity and, in turn, prevent the growth of leukaemia cells. Preliminary experiments using genetic tools have shown that inhibiting METTL1 slows down AML progression, without harming healthy blood cells. Now, the focus is on testing a new small-molecule drug in both laboratory settings and animal models to see if it can effectively and safely target AML.

[1] Haematological Malignancy Research Network (HMRN) – Survival statistics: Acute myeloid leukaemia 2022., https://hmrn.org/statistics/survival

[2] Zhao, P., Xia, L., Chen, D. et al. METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control. Exp Hematol Oncol 13, 8 (2024). https://doi.org/10.1186/s40164-024-00477-8

Project information

Lead researcher

Dr Eliza Yankova

University

University of Cambridge

Blood cancer type

AML

Award type

John Goldman Fellowship

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 What difference will this research make? 

If successful, this research could lead to a new type of treatment for AML that is more precise and less toxic than current options. By specifically targeting METTL1, the therapy could slow down or stop the progression of leukaemia while leaving healthy cells unharmed, reducing the harsh side effects that patients often face with standard treatments. This breakthrough could not only improve survival rates and quality of life for AML patients but also offer hope for developing similar targeted therapies for other cancers in the future.

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