The role of genes in Haematopoietic Progenitor Cell Transplantation
Research type
Research Study
Full title
An investigation of the allelic polymorphism of genetic biomarkers in the context of haematopoietic progenitor cell transplantation outcome.
IRAS ID
234624
Contact name
Paul A Wright
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
The presence or absence of genetic biomarkers is considered when selecting potential donors for Haematopoietic Progenitor Cell Transplantation (HPCT). The investigation will assess the biochemical properties of the proteins encoded by these genes, and the effect of genetic variation on HPCT outcomes. The genes of interest have been chosen due to their high variation within the population.
The study will include several phases:
Clinical Phase
A retrospective study will be carried out, assessing the clinical significance of recipient and donor genes of interest on post-HPCT outcomes within the described time frame. This investigation will involve two cohorts: AML (adult and paediatric) and MPS-1H. High-resolution NGS will be used to sequence five genes of interest in both the recipient and donor, with low resolution presence/absence typing of other relevant genes. These data will be compared against transplant outcomes to assess the clinical relevance of variation in these biomarkers.Biochemical Phase
This study will assess the effect of genetic variation upon the physical activity of the protein encoded by a single gene of interest. To do this, the respective proteins will be isolated and purified. Biochemical techniques will then be used to measure the activity of these proteins. By comparing the activity between the respective proteins encoded by different forms of a single gene (known as 'alleles'), it will be possible to assess the impact of genetic variation on protein activity.Applying Biochemical Study to Clinical Study
The findings of the biochemical study will be used (if possible) to stratify clinical data for further analysis (e.g. genes that encode proteins with weak binding activity versus those with strong binding activity). This will investigate whether these biochemical differences significantly impact upon transplant outcomes. This may lead to development of a novel model for donor selection.A population study will assess gene frequencies using data from all samples tested.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
18/NW/0553
Date of REC Opinion
18 Sep 2018
REC opinion
Further Information Favourable Opinion