The consequences of CHIP mutations

Clonal haematopoiesis of indeterminate potential (CHIP) in healthy individuals increases rapidly from age 60 onwards and has been associated with increased risk for malignancy. CHIP is driven by somatic mutations in stem cells that are implicated in leukaemia. We hypothesize that stem cell fitness substantially contributes to transformation from CHIP to malignancy. Stem cell fitness is defined as the proliferative advantage over cells carrying no or only neutral mutations. The distinct molecular outcome and the resulting altered stem cell fitness due to mutations in different CHIP genes is still not characterized. We aim to use this information in combination with surface proteomics analysis to form the basis for patient stratification.By taking advantage of existing longitudinal cohorts of aging – the Lothian Birth Cohorts (LBC) of 1921 and 1936 - in combination with a novel hematopoietic stem/progenitor cell system this project will identify molecular characteristics of CHIP variants and their effect on stem cell fitness. In a second step we will analyse altered surface proteins respectively to the mutations and will use this to define biomarkers and/or therapeutic vulnerabilities.The aim of this project is to help early detection and monitoring of patients with certain CHIP mutations. Defined therapeutic vulnerabilities goal to prevent transformation to leukemia.

EHA Bilateral Collaborative Grant

Zentrum für Biologische Wissenschaften

University of Glasgow
Funktion: Projektleitung
Abteilung: School of Cancer Sciences