[Transcription factor-based therapies for acute myeloid leukemia]

Transcription factors are proteins that bind specific DNA-regulatory sequences and regulate gene transcription. In a hematopoietic system, transcription factors, such as C/EBPα, PU.1, and RUNX1, regulate the expression of essential genes to maintain the homeostasis in the bone marrow. The dysfunction of transcription factors mediated by gene mutations, chromosomal aberration, or aberrant expression can lead to cancer, including acute myeloid leukemia. Previously, transcription factors were not considered as therapeutic targets; however, a better understanding of cancer pathology and mechanisms underlying transcriptional regulation has enabled us to develop therapeutic agents that target transcription factors. C/EBPα is one of the essential transcription factors responsible for granulocytic differentiation and maturation. CEBPA mutation and/or low C/EBPα expression contribute to the pathogenesis of acute myeloid leukemia. Several therapeutic agents have been developed to increase C/EBPα activity, including ICCB280, which is a small molecule we identified by high-throughput screening. We believe that the novel therapeutic approach of targeting transcription factors will benefit patients with acute myeloid leukemia in the near future.