Can WGTS replace standard-of-care diagnostics in AML?

Whole-genome and -transcriptome sequencing (WGTS) proved useful for the diagnosis and risk stratification of participants with acute myeloid leukaemia (AML). The agreement between results from standard-of-care (SoC) techniques and WGTS was overall good, albeit with some variation in the detection of subclonal features.

Dr Anna Staffas (University of Gothenburg, Sweden) and colleagues investigated whether WGTS reaches the sensitivity and specificity to replace SoC methods in AML diagnostics [1]. The research team analysed data from 129 de novo participants with AML, who mostly received both SoC diagnostics (G-band, FISH, fragment, Sanger, NGS-panel) and WGTS.

WGTS was associated with improved detection of risk-classifying rearrangements, detecting 6 rearrangements that were missed by SoC techniques, in addition to all the rearrangements that were detected by SoC techniques. Whole-transcriptome sequencing confirmed the findings of whole-genome sequencing (WGS). Next, most large copy number variations that were detected by SoC techniques were also detected by WGS. Yet, some subclonal events were detected solely by SoC techniques whereas others were only spotted by WGS. Furthermore, FLT3-ITD status was missed with WGS in 11 out of 42 participants (26%).

“Overall, we noticed a good concordance in AML classification between SoC diagnostics and WGTS, with a 5–7% increase in genetically defined entities with WGTS,” said Dr Staffas. “WGTS detects fusions that are missed with current SoC techniques, whereas (low-frequency) FLT3-ITD may be missed with WGS, indicating that parallel targeted analysis is required,” she concluded.

1. Staffas A, et al. Whole-genome and -transcriptome sequencing as a comprehensive precision diagnostic test in acute myeloid leukemia: a report from the national initiative genomic medicine Sweden. S338, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 2024