NGS-MRD-ALL

The Application of Next generation Sequencing (NGS) to the Analysis of Minimal Residual Disease (MRD) in Childhood Acute Lymphoblastic Leukaemia (ALL)

Summary

There are approximately 400 new cases and 30 relapses of childhood ALL per year in the UK. Critical to the improved outcome of these children has been risk-stratification using a biomarker known as Minimal Residual Disease (MRD). Whilst extremely predictive of outcome, the current method for measuring MRD, (real time quantitative polymerase chain reaction based measurement of patient specific immunoglobulin and T-cell receptor gene rearrangements (Ig/TCR RQ-PCR)) is time-consuming, expensive, requires significant technical expertise, requires analysis of bone marrow samples and fails to give a result in almost 10% of cases. We are planning to develop the current technique for use on an Illumina MiSeq next generation sequencing (NGS) platform. The key goals of our project are to adapt the current PCR methodology so that reproducible and quantitative results are obtained on the Illumina platform, and to develop a novel bioinformatic pipeline that will enable interpretation of the 25 million sequencing reads that this technique generates but that can be easily used by NHS laboratory staff. In achieving these aims we will deliver a cheaper, faster, more sensitive test, with wider patient applicability, whilst also enabling us to further understand the mechanisms of disease relapse.