15 March 2021

Whole genome sequencing is as good as – if not better than – conventional genetic tests to help determine the best treatment for acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), a new US study has reported.

Researchers at the Washington University School of Medicine in St. Louis say not only is whole genome sequence accurate, but it is also cost-effective and results can be delivered in just a few days.

Their findings are published in the New England Journal of Medicine.

Senior author Dr David Spencer, an assistant professor of medicine and medical director of the clinical sequencing facility at the McDonnell Genome Institute, said: “Our study suggests whole genome sequencing is a reliable and practical approach for detecting all of the changes that are important for assessing the risk of relapse for AML and MDS patients, using a single test.

 “This approach can be performed when conventional testing methods are unsuccessful and also could be applied to other cancers, including solid tumours. This means that patients with other cancer types eventually could benefit from rapid clinical genome sequencing.”

Patients with AML and MDS are normally divided into three risk categories based on the results of standard genetic testing. Favourable-risk patients are usually treated with chemotherapy only, unfavourable-risk patients often need more intensive treatment at the time of diagnosis. Treatment for intermediate-risk patients varies, depending on each individual’s state of health, personal preferences, and doctors' guidance.

The researchers evaluated blood samples from 263 patients with AML and MDS and sequenced their entire genomes comparing the results with karyotyping, the traditional genetic test, from the same patients.

They found whole genome sequencing identified all of the same major genomic abnormalities as karyotyping and identified additional genetic abnormalities in 17% of the cases.

Out of the cohort of 263 whose blood samples were tested, 117 were newly diagnosed patients, while samples from the remaining 146 were analysed retrospectively.

For the newly diagnosed patients, whole genome sequencing found additional genetic information in about 25% of the cases, changing the risk category for 19 of them.

The researchers also found that whole genome sequencing could accurately risk stratify patients who had inconclusive results from the traditional karyotype-based analyses. According to the investigators, inconclusive results or assay failures can occur in up to 20% of AML patients.

According to Dr Spencer, most patients whose risk category changed based on the whole genome approach moved into less favourable risk categories, which suggests the approach may more consistently identify patients in the unfavourable-risk category.

Dr Spencer said: “For these types of blood cancers, conventional chromosome analysis is a critical part of the standard diagnostic work-up.

“We know from research studies that whole genome sequencing can detect these types of chromosomal abnormalities, so that part of our study is not terribly surprising. What we showed is that genome sequencing has reached a point that it is now practical, fast, economical, clinically feasible and accessible for the routine testing of patients.”

The researchers will continue to evaluate whole genome sequencing for AML and MDS patients as part of clinical trials.


Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. (2021) “Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers.” New England Journal of Medicine, doi: 10.1056/nejmoa2024534

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