The Evolutionary Dynamics of Pre-Leukaemic Clones in the Blood
Research type
Research Study
Full title
Predicting Acute Myeloid Leukaemia (AML) Earlier by Quantifying Clonal Dynamics in 10 years of Serial Blood Samples from UKCTOCS.
IRAS ID
250270
Contact name
Jamie Blundell
Contact email
Sponsor organisation
University of Cambridge
Clinicaltrials.gov Identifier
HVS/2018/2308, Insurance reference number
Duration of Study in the UK
2 years, 0 months, 30 days
Research summary
CAN WE USE THE EVOLUTIONARY DYNAMICS OF PRE-LEUKAEMIC CLONES IN THE BLOOD TO PREDICT ACUTE MYELOID LEUKAEMIA (AML) EARLIER?
As we age, we acquire genetic changes (mutations) in the cells responsible for blood production (haematopoietic stem cells), a phenomenon termed “clonal haematopoiesis”. Recent studies, using novel sequencing methods, have shown that as many as 95% of healthy individuals over the age of 60 has evidence of clonal haematopoiesis detectable in their blood. We know that this increases the risk of these individuals developing blood cancers, such as Acute Myeloid Leukaemia (AML), but at the moment we are unable to predict which individuals are most at risk.
A number of large studies have been published looking at clonal haematopoiesis in population-based studies (e.g. Jaiswal 2014, Genovese 2014), but the key thing these studies lack is good longitudinal data. In order to determine which individuals are most at risk of developing AML, we need a better understanding of how the growth/ survival of the blood cells harbouring acquired mutations changes over time (the ‘evolutionary dynamics’) and, importantly, how this differs in individuals who subsequently develop AML.
We hypothesize that ‘pre-leukaemic’ blood cells contain multiple ‘driver’ mutations (mutations which give the cell a selective advantage over other cells) and, as a result, groups of these cells (termed ‘clones’) grow more quickly than clones associated with ‘healthy ageing’. By analysing the dynamics of these clones in longitudinal blood samples (which have already been collected over a ~10 year period as part of the UKCTOCs (UK Collaborative Trial of Ovarian Cancer Screening) trial) from ‘healthy’ individuals and from individuals who have subsequently developed AML, we hope to exploit the hypothesised differences in evolutionary dynamics of pre-leukaemic clones in order to identify early hallmarks of AML.REC name
South Central - Berkshire B Research Ethics Committee
REC reference
18/SC/0481
Date of REC Opinion
4 Sep 2018
REC opinion
Favourable Opinion