Among patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), whole-genome sequencing may be superior to conventional cytogenetic analysis for risk stratification, according to research published in The New England Journal of Medicine.

Genomic analysis is increasingly becoming a mainstay of personalized medicine, with genomic analysis used across cancer subtypes to help stratify patients by likelihood of therapy response and disease aggressiveness. The genomic landscape of cancers is, furthermore, frequently changing, with mutations from a variety of causal events contributing to clinical decision-making.

Genetic deviations from the wild-type are of increasing importance in the AML and MDS settings, in both the World Health Organization AML genomic classification system and the MDS revised International Prognostic Scoring System. While cytogenetic analysis has, historically, been the mainstay profiling tool of these systems, technological improvements have made whole-genome sequencing a viable alternative.


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For this study, researchers “developed a streamlined approach to whole-genome sequencing for genomic profiling of patients with AML or MDS and applied it to diagnostic clinical samples in real time to evaluate its feasibility, accuracy, and utility in the clinical setting.”

Data from 263 patients with myeloid cancer, among whom 235 had previously undergone cytogenetic analysis, were included in the overall population; 146 and 117 were included in a retrospective and prospective cohort, respectively. In the retrospective vs prospective cohort, 107 vs 68 patients had AML, respectively, the median age was 53.7 vs 60.6 years, and 47 (44%) vs 30 (44%) patients were female sex.

A total of 40 recurrent translocations and 91 copy-number alterations previously detected by cytogenetic analysis were similarly detected by whole-genome sequencing. In 17% (40) of patients in the overall population, previously unnoted genomic events of clinical relevance were detected.

In the prospective cohort, sequencing was complete in a median of 5 days, and provided new information leading to a patient-risk category change in 19 (16.2%) patients. Risk groupings of AML patients as determined by whole-genome sequencing, furthermore, were predictive of clinical outcomes.

The authors noted, finally, that while these results were applicable only to patients with AML or MDS, future research may show that whole-genome sequencing is similarly efficient and beneficial in other cancer subtypes.

Disclosure: Several study authors declared affiliations with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.

Reference
Duncavage EJ, Schroeder MC, O’Laughlin M, et al. Genome sequencing as an alternative to cytogenetic analysis in myeloid cancers. N Engl J Med. 2021;384(10):924-935. doi:10.1056/NEJMoa2024534