Clinical implementation of Germline testing for myeloid neoplasms: results from a prospective Swedish Cohort study
Recognition of germline predisposition in hematological malignancies is one of the most significant recent advancements in the field of hematology. A recent Swedish study shows that germline investigation based on the Nordic guidelines is feasible and has a great impact on the clinical decision for these patients.
Panagiotis Baliakis. Photo: Ulrika Gunnarsson
Up to 13% of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) harbor germline predisposition to myeloid neoplasms. Nordic guidelines for management of patients with suspected germline predisposition for myeloid neoplasms were published in 2019. The present prospective observational study aimed to validate these guidelines and provide a solid basis for clinical implementation.
In this study, applying the Nordic guidelines resulted in an overall diagnostic yield of 35%, (higher of that of similar guidelines in other hereditary cancer forms). The study provides solid evidence that implementation of the Nordic guidelines on germline predisposition for myeloid neoplasms in the clinical setting has a significant impact. With that being said, further research is warranted in order to elucidate the mechanisms in families with suspected predisposition for blood cancer where the application of the Nordic guidelines failed to identify an underlying genetic explanation says
, Panagiotis Baliakas, senior physician and director of Clinical Genomics Uppsala.
The study was performed in the context of a national collaboration among geneticists and hematologists with interest in germline predisposition for hematological malignancies.
In conclusion the validation of the Nordic criteria-based guidelines provides an important framework enabling the establishment of solid clinical routines.
This study is a great example of how modern sequencing technologies can generate the necessary information for diagnostic recommendations. The exome sequencing analysis that was used in this study was developed by Clinical Genomics Uppsala and is one of several different analyses that we run in collaboration with Uppsala University Hospital
, says Claes Ladenvall, Head of Bioinformatics at Clinical Genomics Uppsala.
Publication
Bianca Tesi, Anna Robelius, Berivan Baskin, Vladimir Lazarevic, Stefan Deneberg, Martin Höglund, Linda Fogelstrand, Johanna Ungerstedt, Tatjana Pandzic, Magnus Tobiasson, Hege Gravdahl Garelius, Ekaterina Kuchinskaya, Fredrik Persson, Helena Ågerstam, Helene Hallböök, Thoas Fioretos, Jessika Nordin, Anna Norberg, Ann-Charlotte Thuresson, Sören Lehmann, Claes Ladenvall, Gisela Barbany, Lovisa Vennström, Elisabeth Ejerblad, Lucia Cavelier, Jörg Cammenga, Martin Jädersten, Eva Hellström-Lindberg, Panagiotis Baliakas; Validation of Guidelines for Genetic Investigation of Myeloid Neoplasms with Germline Predisposition: Results from a Prospective Cohort Study. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-4251