Association of the RUNX1/AML1 Gene Mutation and Familial MDS/AML: A Case Report and Review of Literature

Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) are mostly sporadic hematopoetic malignancies, which generally thought inheritable, though specific gene abnormalities may play a role in the progression of myelodysplasia. Recently, many reports have revealed that mutations in the RUNX1/AML1 gene are involved in defective hematopoiesis. Moreover, patients with such mutations have a significant poorer prognosis than cases without RUNX1 mutations. Since familial occurrence of MDS/AML is rare, there are few reports about the relationship between RUNX1 mutations and familial MDS/AML. In the study of a familial MDS/AML, we found a61-year-old male with MDS who developed into AML later. He had a history of leukocytopenia and thrombocytopenia for decades before developing into pancytopenia. We identified a RUNX1mutationin this patient through sequencing. Furthermore, the same mutation was present in his son (II-1) who suffered from MDS as well as his granddaughter. Intriguingly, II-1 was 10years old when diagnosed with MDS, nearly 50 years earlier than his father. Myelodysplastic features in bone marrow sections of these two patients were not obvious in the early stage. They mainly showed active erythrocyte proliferation, together with an increased mean corpuscular volume, which can indicate inflection points in MDS progression. To date, patients with familial MDS had no antecedent hematological abnormalities in the early stage. In this study, we found a new inheritable mutation of the RUNX1 gene in the familial MDS which is frequently deregulated in hematological malignancies. As RUNX1 was present in the early stage of familial MDS, this genetic mutation may serve as an early diagnostic marker and contribute to the treatment of MDS/AML.