Genomic analysis of a familial myelodysplasia/acute myeloid leukemia and inherited RUNX1 mutations without a pre-existing platelet disorder.

Both I RUNX1 i and I TP53 i mutations were already present in the PB DNA of patient II.5 at least one year before diagnosis, although the 5q deletion present at diagnosis was not detected. Additionally, we sequenced a posttransplant sample from patient II.5 in CR with positive MRD and detected the same mutations as in the diagnostic sample, but at lower allele frequencies: 2.7% I RUNX1 i p.L56S and 2% I TP53 i p.G245D. Although the reason why the second mutation occurred in I TP53 i in both patients is unknown, previous studies have demonstrated a cooperation between I RUNX1 i and I TP53 i . In addition, findings from this family add to the existing evidence that I RUNX1 i is a highly penetrant leukemia predisposing gene and that I TP53 i mutations are the final leukemia-causing event. [Extracted from the article]