"Clearly, the most efficient approach [for myeloid and lymphoid testing] is to have, as far as possible, everything going down one streamlined pathway.”
Joanne Mason, Head of Haemato-oncology, West Midlands Regional Genomics Laboratory
Haematological cancer is the fifth most common cancer in the UK. Over 41,000 people are diagnosed every year and approximately 250,000 people live with blood cancer in the UK1. Successful treatment and improved prognosis is directly impacted by the speed and efficacy of diagnosis1. Given their inherent complexity, the analysis of haematological malignancies requires an interrogative and iterative testing approach, often across multiple different platforms. This, combined with the ever-expanding number of targets that are important across both myeloid and lymphoid malignancies has established a clear need to streamline workflows into one single test.
To address this, in collaboration with Nonacus, Joanne Mason, Head of Haemato-oncology at the West Midlands Regional Genetics Laboratory, has developed a targeted NGS panel, that can detect SNVs, indels and CNVs in genes associated with both myeloid and lymphoid neoplasia. The resulting test has huge advantages for her laboratory in the reduction of turnaround times and cost burdens associated with multi-testing approaches.
Nonacus spoke to Joanne Mason, Head of Haemato-oncology at the West Midlands Regional Genomics Laboratory in Birmingham, UK, to find out more:
Could you tell us about your clinical service?
Our lab delivers a comprehensive genomic testing service across a range of myeloid and lymphoid malignancies. The population covered by the West Midlands Regional Genomics Laboratory comprises about 6 million people, so we're a very busy, large laboratory. We use a variety of different techniques to assist with the diagnosis, prognostication, disease monitoring and treatment identification for haemato-oncology patients.
What prompted the need for a pan-haematological NGS solution?
There are an extensive number of targets that are important for both myeloid and lymphoid haematological malignancies, that currently must be tested for using a wide range of different strategies. Clearly, the most efficient approach is to have, as far as possible, everything going down one streamlined pathway. The capabilities of NGS to detect single nucleotide variants, copy number variants and structural variants associated with both myeloid and lymphoid neoplasia, lends itself to developing a single strategy for streamlined malignancy testing.
Could you tell us about the panel design strategy?
The panel design strategy involved inclusion of the clinically relevant test directory targets necessary for both myeloid and lymphoid neoplasia.
In particular, there were specific genes that we were interested in exploring in more detail, including KMT2A (MLL-1). For prognostic reasons, we wanted to ensure that we could detect partial tandem duplications and rearrangements in this gene, so in the design we tiled across the intronic regions, to support comprehensive detection of these events for KMT2A.
We also wanted to ensure coverage of U2AF1, which has recently been reported as significant in paediatric acute myeloid leukaemia (AML), again involving partial tandem duplications.
What were your FLT3-ITD requirements for the design?
We wanted to ensure that we could detect partial tandem duplications in FLT3-ITD. That is why we tiled across intron 14 of this gene in the panel design process; by doing so, we have been able to detect FLT3-ITD duplications in excess of 200 base pairs. We have validated this result by comparing it to orthogonal techniques.
How will this impact your clinical service?
An important feature to ensure the efficiency of our clinical service is automation of technical processes. It was important to us that we could set up the pan-haematological NGS solution as an automated process in our lab. We have worked with Nonacus to develop a program for our Hamilton robot, such that this panel can automate hybridisation capture steps for enrichment, enabling us to process 96 samples at a time; the resulting impact for our clinical service is time and cost-effective testing of haematological malignancies.
What is your vision for the future of haematological testing?
Following on from finding important targets for diagnosis and prognosis of haematological malignancy, the next area of development is to find targets to enable monitoring of measurable residual disease. This is currently offered to AML patients, but it is something that we are actively looking to develop and hopefully will be something that can be extended to all patients in the future.