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New study could lead to a one-stop shop test for AML and MDS diagnosis

The Bloodwise logo. Bloodwise appears in black text against a white background
Posted by
12 Jul 2016

The diagnosis of acute myeloid leukaemia (AML), one of the most aggressive blood cancers, involves a series of complex tests to analyse various features of the disease’s genetic signature. But a new piece of research funded in-part by Bloodwise shows it may be possible to replace these with a single test that can quickly and accurately diagnose and guide treatment.

AML diagnosis

Blood cancers are caused when errors creep in to the DNA code of developing blood cells, disrupting key genes involved in the normal controls on cell growth. The exact makeup of a patient’s genetic faults, including knowing which ones are driving the disease and which ones are the result of it, can determine its aggressiveness, how sensitive it is to treatment and the chances of it returning following remission. This can make the task of providing an accurate diagnosis and predicting a patient’s outlook difficult.

International guidelines currently require hospital laboratories to screen for at least three classes of genetic alteration, using separate methods to prepare and analyse samples. This is both a technically demanding and time-consuming process, but essential as we move towards a tailored treatment plan for each patient.

1 test to diagnose AML?

This new study, published in the leading international journal Blood, could mark a major step forward for blood cancer diagnostics by using a one-stop shop method to identify patients with diverse sub-types of AML and the related condition myelodysplastic syndrome (MDS). The current array of tests used at diagnosis detect many types of genetic fault – large-scale rearrangements of chromosomes, sequences of DNA that have been added, deleted, duplicated or flipped around, and changes to single letters that make up the DNA code. These results can flag patients who are most likely to benefit from certain targeted drugs, those who may need more intense chemotherapy or a stem cell transplant, and those in whom it’s possible to monitor the disease to track treatment response.

But rather than going through the variety of time, cost and labour-intensive laboratory tests, a collaborative team of international scientists led by Dr George Vassiliou at the Cambridge-based Wellcome Trust Sanger Institute have created a tool that only needs a small DNA sample to produce the same genetic snapshot of the leukaemia. A key development was being able to run a suite of analyses in parallel, which allowed simultaneous detection of the various genetic abnormalities.

The researchers took advantage of cutting-edge next-generation DNA sequencing, which is becoming ever-more fast and affordable, and combined this with open-source computational tools to achieve a 100% accurate picture for most types of abnormality. Although this study only represents an initial proof of principle, it does provide an encouraging glimpse of what the future may look like for diagnosis and tailored treatment of AML, MDS and other blood cancers.

What's next?

Despite the success in simplifying the approach, getting to this stage was anything but easy. The setup required significant effort and technical skill to hone the sample preparation, genetic tagging and computational analysis. This level of expertise may currently hinder the widespread rollout of such tools, and so the researchers will need to optimise the system to make it suitable for general use. 

In addition, although the new system was impressive in its level of accuracy, it didn’t incorporate every genetic change that has been associated with AML or MDS. This is likely to be overcome, which will be an important step towards its use in standard diagnostics.

This type of work is particularly important because understanding the genetic profile of every patient’s disease is critical to both their prognosis and treatment. As highlighted in our recent blog, the different combination of genetic faults in AML patients results in markedly different long-term prospects and predicts response to available treatments. This is also true for many of the other 137 forms of blood cancer. This new approach could be adapted to screen for genetic abnormalities across different blood cancers, enhancing the speed and accuracy of diagnosis for optimum treatment.

The success of this study serves to highlight how continued investment in research can provide tangible results that are moving us into an era where precision medicine is a reality for blood cancer patients.

  • The study was published in Blood: McKerrell, et al. “Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies”, Blood 2016 128:e1-e9; doi:10.1182/blood-2015-11-683334. A commentary is provided by Dillon & Grimwade in the same edition.
  • The research was funded by Wellcome Trust, Bloodwise, Kay Kendall Leukaemia Fund, Medical Research Council and the Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal.

Photo credit: iStock

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