George VassiliouPhD, MD
Wellcome Trust Sanger Institute
Project Term: July 1, 2018 - December 31, 2022
Here we propose to study blood DNA from 1500 people who have had extensive genetic and aging-related tests over many years as participants of the "Immunoageing" study (http://www.immunoageing.eu/index.html). We propose to study these people for the presence of age-related clonal hematopoiesis (ARCH) to understand what factors are associated with ARCH and its expansion. Our aim is to use these findings to help prevent ARCH from progressing to myeloid cancer in at risk individuals identified by future screening programs, which we and others developing separately.
Myeloid cancers are a range of related neoplasms, including the myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Collectively, they affect 8-10 per 100,000 individuals per year and are lethal to the majority, as therapies for myeloid cancers have changed little for 25-30 years and prevention programs are entirely lacking. Advances in DNA sequencing have shown that these cancers are caused by mutations in similar/overlapping genes. Furthermore the phenomenon of age-related clonal hematopoiesis (ARCH) was recently identified and found to be the ancestor of all myeloid cancers. ARCH is common and constitutes a benign growth of cells that arise from a single blood stem cell. It affects more than 10% of people aged over 60 years without causing any noticeable symptoms. However, a small proportion of people with ARCH progress to cancer and currently we do not understand why this happens to them and not others. Our team found that ARCH cells expand better in certain people and that this may be influenced by factors related to aging of the blood or other systems in the body that affect blood growth.