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

<jats:title>Abstract:</jats:title><jats:p><jats:bold>Objective:</jats:bold> Acquired somatic point mutations in <jats:italic>RUNX1/CBFA2/AML1</jats:italic> 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 <jats:italic>RUNX1</jats:italic> 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 <jats:italic>ATRX</jats:italic> gene, have an especially high incidence of <jats:italic>RUNX1</jats:italic> mutations.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We analysed samples from 78 patients for <jats:italic>RUNX1</jats:italic> point mutations by denaturing high‐performance liquid chromatography (DHPLC): 26 with MMM and 52 with MDS, including 18 with ATMDS.</jats:p><jats:p><jats:bold>Results: </jats:bold> We found five <jats:italic>RUNX1</jats:italic> 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 <jats:italic>RUNX1</jats:italic> point mutations (2/18, 11.1%) when compared with MDS without thalassaemia (3/34, 8.8%; <jats:italic>P</jats:italic> = 0.58).</jats:p><jats:p><jats:bold>Conclusion: </jats:bold> <jats:italic>RUNX1</jats:italic> point mutations are common in high‐risk MDS, but not in MMM. DHPLC is a useful technique for high‐throughput analysis of <jats:italic>RUNX1</jats:italic> mutation status in myeloid disorders, and may be complementary to screening via other methods.</jats:p>