Frequency and Clinicopathologic Features of RUNX1 Mutations in Patients With Acute Myeloid Leukemia Not Otherwise Specified.

Objectives: To evaluate the frequency and clinicopathologic characteristics of RUNX1 mutations, focusing on patients with acute myeloid leukemia not otherwise specified (AML NOS).

Methods: Diagnostic samples from 219 patients with AML NOS were analyzed for RUNX1 mutations using standard polymerase chain reaction and direct sequencing.

Results: Thirty-one RUNX1 mutations were detected in 33 (15.1%) patients. Mutations clustered in the Runt homology (61.3%) and transactivation domains (25.8%). Frameshift mutations were most common (51.6%), followed by missense (41.9%) and nonsense (6.5%) mutations. Patients with RUNX1 mutations had a lower platelet count (P = .013) and shorter relapse-free survival (P = .045) than those without. The presence of RUNX1 and NPM1 or CEBPA mutations was mutually exclusive. A literature review, including our study, showed that patients with RUNX1 mutations were associated with intermediate risk; coexisting mutations such as FLT3-ITD, ASXL1, TET2, and DNMT3A; and a relatively cytogenetic heterogeneity.

Conclusions: Our findings strengthen previous data concerning RUNX1 mutations in AML and support the notion that RUNX1 mutational status should be integrated into a diagnostic workup of AML, particularly for AML NOS or an intermediate-risk group.