The evolution of myelodysplastic syndrome +/- progression to AML
Research type
Research Study
Full title
A longitudinal multi-omic approach to understanding the development of myelodysplastic syndrome (MDS) and its evolution towards acute myeloid leukaemia (AML)
IRAS ID
348793
Contact name
Caroline Watson
Contact email
Sponsor organisation
University of Cambridge
Duration of Study in the UK
3 years, 11 months, 30 days
Research summary
USING BLOOD SAMPLES COLLECTED OVER TIME FROM INDIVIDUALS WHO LATER DEVELOPED MYELODYSPLASTIC SYNDROME (MDS) +/- ACUTE MYELOID LEUKAEMIA (AML), THIS PROJECT AIMS TO UNDERSTAND HOW AND WHY MDS DEVELOPS AND WHAT DRIVES ITS PROGRESSION TO AML.
Acute myeloid leukaemia (AML) is an aggressive blood cancer which claims the lives of 70-80% of patients within 5 years of diagnosis. Like many cancers, AML typically develops via serial acquisition of mutations (DNA changes) in cells: a process that starts years before diagnosis. This raises the hope that we may be able to catch the disease in its early stages and stop it from becoming full-blown AML. However, this requires both accurate prediction of those at highest risk and the ability to prevent the disease therapeutically. Accomplishing either demands a deeper understanding of the mechanisms driving AML development. In recent years we have improved our ability to identify individuals at ‘higher-risk’ of AML, but how and why AML develops in only some of these higher risk individuals remains poorly understood.
This study focuses on a group of individuals who developed myelodysplastic syndrome (MDS), a blood disorder associated with high-risk of developing AML. Leveraging the unique opportunity provided by longitudinal blood samples already collected from these individuals, prior to their diagnosis of MDS+/-AML, we will perform ultra-deep DNA sequencing to study the dynamics of mutant pre-leukaemic clones. By integrating these findings with proteomic, miRNA and epigenetic changes over time, we seek to understand the disease’s evolution in the years preceding diagnosis. This longitudinal multi-omic analysis will enable us to comprehensively study the evolution of disease and how it differs in those whose MDS does, or does not, progress to AML.
Understanding the evolutionary processes that precede MDS+/-AML will be invaluable for developing AML early detection tools and potentially preventable therapeutic interventions.
REC name
Wales REC 3
REC reference
24/WA/0361
Date of REC Opinion
4 Dec 2024
REC opinion
Favourable Opinion