Panagiotis Baliakas

Rapid genetic characterization of acute myeloid leukemia (AML) is essential for risk stratification and treatment selection. We developed and clinically implemented a targeted Oxford Nanopore Technologies long-read sequencing assay for simultaneous analysis of NPM1, FLT3, IDH1, IDH2 , and TP53 . In 36 patients, the assay detected 63/64 previously identified variants (98.4% sensitivity), including FLT3-ITDs. All TP53 variants in independent cohorts were detected and phased, enabling assessment of allelic status. Prospective validation in a clinical setting showed 100% sensitivity and specificity, with a mean turnaround time of ~ 32 hours, supporting streamlined AML diagnostics and patient management.

High‐throughput sequencing has transformed clinical diagnostics of rare diseases (RD), cancer and infectious diseases by enabling the identification of disease‐causing genetic alterations and facilitating individualised treatment and care. In response to these advances, Genomic Medicine Sweden (GMS) was established in 2017 as a national collaborative effort to accelerate implementation of genomics‐based precision medicine within Sweden's regionally organized, publicly funded healthcare system. GMS brings together the seven university healthcare regions and their associated medical faculties, in collaboration with healthcare regions across Sweden, Science for Life Laboratory, patient organizations, industry and governmental agencies. Activities are coordinated through national disease‐specific expert groups, supported by cross‐cutting functions in bioinformatics, health economics, ethics, education and patient engagement. At the operational level, seven Genomic Medicine Centres, embedded at university hospitals, develop and deliver harmonised genomic diagnostics nationwide. The National Genomics Platform provides secure infrastructure for large‐scale data storage, analysis, and national and international data sharing. Following initial project‐based funding, GMS now receives long‐term governmental support. This review describes the national implementation of genomic‐based precision diagnostics, discusses challenges and lessons learnt, and highlights key milestones across disease areas, including whole‐genome sequencing in RD and paediatric cancer, comprehensive genomic profiling of haematological malignancies and solid tumours, pathogen genomics in microbiology, pharmacogenomic testing and emerging applications of polygenic risk scores in complex diseases. Collectively, these efforts have contributed to more than 500,000 genomic tests being performed within Swedish healthcare between 2017 and 2025. Finally, we outline future diagnostic needs and priority areas to ensure sustainable, scalable and equitable access to precision medicine.

Background: Genomic profiling of patients with myeloid neoplasms (MN) may detect variants with high variant allele frequency (VAF), indicating potential germline origin. All current guidelines recommend further investigation of such variants. Objective: To define the proportion of variants with suspected germline origin that prompted germline investigation in patients evaluated for MN in the clinical setting. Methods: We included 738 patients investigated for MN in Mid‐Sweden between May 2020 and January 2023 with available sequencing data in genes of interest (GOI) according to the Nordic and other international guidelines. Results: In total, 90 patients (12%) carried pathogenic/likely pathogenic (P/LP) variants in GOI according to the Nordic guidelines, with TP53 , RUNX1 , and NRAS being the most common ( n = 37, n = 27, and n = 9, respectively). The potential germline origin was investigated in 16/90 (18%) patients. Two patients (2/16, 12.5%) with germline variants were identified ( DDX41 and RUNX1 , n = 1, respectively). In patients treated with allogeneic stem‐cells transplantation ( n = 15) the investigation rate was higher (7/15, 47%, p < 0.005) compared to the non‐transplanted ones. Applying the European Leukemia Net (ELN) guidelines the number of patients with variants in GOI increased up to 177 mainly due to the inclusion of TET2 , while application of other international guidelines leads to similar results with the Nordic ones. Conclusion: We report a low investigation rate for variants of suspected germline origin detected during the genomic profiling of patients investigated for MN in the clinical setting. Our study underscores the need for further awareness regarding germline investigation for hematological malignancies. Trial Registration : The authors have confirmed clinical trial registration is not needed for this submission.