AML1/RUNX1 gene point mutations in childhood myeloid malignancies

Currently, it is widely accepted that one of the crucial players in adult leukemic transformation is the RUNX1 gene. However, there is little data available regarding whether mutations in this gene also contribute to pediatric leukemia, especially in childhood myeloid malignancies. Therefore we made a decision to screen patients with pediatric myeloid neoplasias for the presence of RUNX1 mutations in their samples.

Patients (n = 238) with diagnoses of de novo acute myeloid leukemia (AML) (n = 198), de novo myelodisplastic syndrome (MDS) (n = 16), therapy-related AML (n = 9), juvenile myelomonocytic leukemia (JMML) (n = 15) were included in this study. All patients were Belarusians between the ages of 0 and 18 years.

The frequency of RUNX1 point mutations in the total group of patients with de novo AML was 3% and de novo MDS was 15%. Cooperation of point mutations in the RUNX1 and NRAS genes, and the cytogenetic abnormality, -7/7q-, was demonstrated in children with therapy-related AML. RUNX1 point mutations predominate in those de novo AML and MDS patients with a normal karyotype in leukemic cells. Frequency of RUNX1 point mutations was about 4% in a group of children with de novo AML aged 0-14 years diagnosed during the period of 1998-2009.

During the course of this investigation, valuable data were obtained concerning RUNX1 gene mutation frequencies in different clinical, morphological, and cytogenetic groups of patients with myeloid malignancies, and its cooperation with other molecular aberrations.