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Cytogenetic analysis, in tandem with targeted gene mutation assessment, is essential for determining prognosis and treatment stratification in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Investigators developed a whole-genome sequencing (WGS) assay that could be completed in a median of 5 days, making it potentially useful for clinical application of risk-adapted therapy. They compared the WGS findings with standard cytogenetic analysis and targeted sequencing of selected myeloid malignancy–relevant genes.
WGS was completed for 263 patients with MDS or AML (146 retrospective and 117 prospective samples) at a single center, 235 of whom also had successful cytogenetic analyses, including fluorescent in situ hybridization (FISH). Cytogenetics and FISH identified 40 recurrent translocations and 91 copy-number alterations, all of which also were identified by WGS. In addition, new relevant genomic events were identified by WGS in 40 of 235 patients (17%). Among the 117 prospectively analyzed patients, relevant new information was identified by WGS in 29 (25%) and led to altered risk categorization in 19 (16%). The authors project the cost of WGS will soon approach that of currently utilized diagnostics.
Duncavage EJ et al. Genome sequencing as an alternative to cytogenetic analysis in myeloid cancers. N Engl J Med 2021 Mar 11; 384:924. (https://doi.org/10.1056/NEJMoa2024534)
Comment
Management of AML and MDS has evolved rapidly in recent years, with reliance on molecular diagnostics to risk-adapt therapy and improve patient outcomes by allowing accurate application of targeted agents, such as FLT3 inhibitors. The WGS assay described here, with its efficient turnaround time, is able to more fully define individual patient risk by providing relevant, and in some cases critical, pharmacogenomic information that can inform treatment optimization. Further prospective validation of the assay at other centers and in prospective clinical trials will be of great interest.