Professor George Vassiliou

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Professor George Vassiliou

Leukaemic & preleukaemic haemopoietic stem cells

Email: gsv20@cam.ac.uk     |     Departmental Affiliation: Haematology

Research       

Plain English: Blood stem cells live in the bone marrow and are responsible for the production of the cells of the blood and the immune system. Like all cells, blood stem cells accumulate random DNA mutations with time in every one of us. Unfortunately, in some people these changes affect genes that make the stem cells grow uncontrollably leading to the development of Acute Myeloid Leukaemia (AML), an aggressive cancer that kills more than 7 out of 10 sufferers. Our group investigates many aspects of AML from how it develops, how we can identify people at risk and how gene mutations change AML cells to make them grow abnormally. Importantly, we have also developed approaches to identify the genetic "weaknesses" of AML in order to develop new treatments against this and related cancers.

Research Focus: The Vassiliou Group seeks to understand the cell-autonomous and cell-non-autonomous processes involved in transformation of normal to leukaemic haemopoietic stem cells and to identify genetic vulnerabilities of myeloid malignancies that can be exploited as targets of novel anti-leukaemic therapies.　

To achieve these aims the group uses three main approaches:　

• Application of genetic screens to identify and investigate genetic vulnerabilities of acute myeloid leukaemia and related cancers in order to develop new therapeutic approaches
• Generation and study of bespoke mouse models of somatic mutation drivers of myeloid malignancies, in order to define their molecular, genomic and phenotypic effects on haemopoietic stem and progenitor cells
• Detection and tracking of the evolution of clonal haematopoiesis in healthy individuals, in order to understand the factors involved in leukaemic progression and develop new approaches for early detection.

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Vassiliou Group photo

Selected Publications

1. McLoughlin MA et al. Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis. Nat Genet. 57:2215-2225 (2025).
2. Gozdecka M et al. Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis. Nature 642:431-441 (2025).
3. Damaskou A et al. Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AML. https://doi.org/10.1182/blood.2024026113 Blood 146:1239-1252. (2025).
4. Wen S et al. Comparative analysis of the Mexico City Prospective Study and the UK Biobank identifies ancestry-specific effects on clonal hematopoiesis. Nat Genet 57:572-582 (2025).
5. Gu M et al. Multiparameter prediction of myeloid neoplasia risk. Nat Genet.1523-30 (2023).
6. Cheloor Kovilakam S et al. Prevalence and significance of DDX41 gene variants in the general population. Blood (2023).
7. Kar SP et al. Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis. Nat Genet 54, 1155-1166 (2022).
8. Fabre MA et al. The longitudinal dynamics and natural history of clonal haematopoiesis. Nature 606, 335-342 (2022).
9. Gozdecka M et al. UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. Nat Genet 50, 883-894 (2018).
10. Abelson S et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 559, 400-404 (2018).
11. Barbieri I et al. Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature 552, 126-131 (2017).
12. Tzelepis K et al. A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia. Cell Rep 17, 1193-1205 (2016).
13. McKerrell T et al. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep 10, 1239-1245 (2015).
14.  Vassiliou GS et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat Genet 43, 470-475 (2011).