ESH MDS 2024 | The role of NGS in MDS diagnosis
Klaus Metzeler, MD, University of Leipzig, Leipzig, Germany, provides insight into his talk on the role of next-generation sequencing (NGS) in the diagnosis of myelodysplastic syndromes (MDS). Dr Metzeler highlights the challenges with differentiating between MDS and clonal cytopenia of undetermined significance (CCUS)/ idiopathic cytopenia of undetermined significance (ICUS) and discusses an investigation into whether NGS can aid in this differentiation. As there are no clear genetic criteria (e.g., specific gene mutations, allele frequency, number of mutations) for these entities, Dr Metzeler concludes that, at present, a fraction of MDS still requires the use of a morphological exam for its accurate diagnosis. This interview took place at the European School of Hematology 9th Translational Research Conference on Myelodysplastic Syndromes (ESH MDS) in Budapest, Hungary.
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Transcript (edited for clarity)
We had a fantastic meeting at the ESH in Budapest and an intensive discussion on the various diagnostic tools to diagnose MDS, and I was particularly looking into the role of next-generation sequencing. And as the audience will be aware, the current diagnostic criteria for MDS, at least according to the WHO classification, require morphologic dysplasia to be seen under the microscope, and that in some cases can be challenging...
We had a fantastic meeting at the ESH in Budapest and an intensive discussion on the various diagnostic tools to diagnose MDS, and I was particularly looking into the role of next-generation sequencing. And as the audience will be aware, the current diagnostic criteria for MDS, at least according to the WHO classification, require morphologic dysplasia to be seen under the microscope, and that in some cases can be challenging. There will be some patients who have cytopenia, which is the other diagnostic criterion, but they will not have clear-cut, unequivocal morphologic dysplasia. If patients have no dysplasia at all, they would be classified as CCUS, clonal cytopenia of uncertain significance, or ICUS, idiopathic cytopenia of uncertain significance, depending on whether or whether they don’t have a mutation on NGS. So, we have this category of clonal cytopenias without dysplasia, CCUS, and we have MDS, and the distinction between those two is dysplasia on the microscopic examination. And then the question is, can genetic criteria help us also draw a line between these two conditions? And we looked at that data a little bit more in detail and it actually comes out that no simple criterion, such as which gene is mutated, what is the size of the clone (the allele frequency), what is the number of mutations, all these things, there are subtle differences between CCUS and MDS, but nothing allows us to draw a clear line and say, if you have that mutation, it must be MDS. Or if the clone has that size, it must be MDS. There’s a broad overlap between CCUS and MDS. So that means morphology actually still has an important role in diagnosing MDS. There’s also a fraction of MDS patients that have no mutations at all on an NGS test. Some of them also have no blast elevation, no abnormal cytogenetics. So there is still a small but…there’s a fraction of MDS that really the diagnosis relies on the morphologic exam. Whether that will in the future change when we move from sequencing gene panels to sequencing whole exomes/whole genomes, still remains to be seen. Yeah, that was that was the topic of my talk at the ESH meeting.
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Disclosures
Consultancy: Celgene/BMS, Janssen, Novartis, Otsuka, Pfizer; Honoraria: AbbVie, Astellas, Celgene/BMS, Janssen, Menarini StemLine, Novartis, Pfizer.
