Frequency and Functional Characterization of RUNX1 Germline Variants in Myeloid Neoplasms

Current estimates suggest that up to 10% of patients with myeloid neoplasms (MN) harbor variants associated a germline predisposition. A pathogenic variant in the runt-related transcription factor 1 gene (RUNX1) is frequent cause predisposition MN. RUNX1 detected tumor tissue at VAF close 50% are potentially and causative familial platelet disorder malignancies. Previous studies have found 3% acute leukemia; however, frequency less advanced has not been examined. We screened 590 suspected MN, excluding myeloproliferative neoplasms, for RUNX1. 83 (14%) by targeted sequencing tissue. In 40 (6.8%), was above 30%. 32 patients, skin biopsies were available used Sanger assess status. Two tested (6.3%) confirmed as germline, both curated unknown significance. To further explore pathogenicity these variants, we implemented novel CRISPR-Select functional genetic assay. The assay demonstrated profound effect on proliferation K562 cells known but no two study. therefore propose classified likely benign. this study, show rare Danish MN use classification variants.