Somatic point mutations in RUNX1/CBFA2/AML1 are common in high-risk myelodysplastic syndrome, but not in myelofibrosis with myeloid metaplasia

Objective: Acquired somatic point mutations in RUNX1/CBFA2/AML1 have recently been described in a subset of patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Given the importance of core-binding factor in megakaryocytic differentiation and platelet production, as well as the central role of megakaryocytes in the pathophysiology of myelofibrosis with myeloid metaplasia (MMM), we hypothesised that RUNX1 gene mutations might be common in MMM. In addition, it is unclear whether patients with MDS-associated acquired alpha thalassaemia (ATMDS), a special subgroup with a very high incidence of point mutations in the ATRX gene, have an especially high incidence of RUNX1 mutations. Methods: We analysed samples from 78 patients for RUNX1 point mutations by denaturing high-performance liquid chromatography (DHPLC): 26 with MMM and 52 with MDS, including 18 with ATMDS. Results: We found five RUNX1 mutations in MDS patients (9.6%), all of whom had RAEB-2 or a history of treated AML, but none in MMM patients. ATMDS patients did not have an increased risk of RUNX1 point mutations (2/18, 11.1%) when compared with MDS without thalassaemia (3/34, 8.8%; P = 0.58). Conclusions: RUNX1 point mutations are common in high-risk MDS, but not in MMM. DHPLC is a useful technique for high-throughput analysis of RUNX1 mutation status in myeloid disorders, and may be complementary to screening via other methods.