MYB proto-oncogene, transcription factor mRNA (MYB mRNA)

The MYB proto-oncogene, transcription factor mRNA (MYB mRNA) serves as the template for the c-Myb protein, a key regulator of hematopoietic cell proliferation and differentiation (UniProt P01106). MYB is highly expressed in immature hematopoietic cells and is essential for maintaining the stem cell pool, but its expression must be downregulated for terminal differentiation to occur (Ramsay and Gonda, 2008, Nature Reviews Cancer). In many cancers, particularly acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC), MYB is constitutively overexpressed or altered through gene fusions, driving uncontrolled cell growth and survival (Andersson et al., 2020, Leukemia). Because the c-Myb protein lacks a conventional small-molecule binding pocket, it has been historically labeled as undruggable, leading to the development of therapies that target its mRNA or pre-mRNA. Antisense oligonucleotides (ASOs), such as ION251 (IONIS-MYB-2.5Rx), are designed to bind specifically to MYB mRNA and trigger its degradation via RNase H, thereby reducing the production of the oncogenic protein (ClinicalTrials.gov NCT04320615). This approach aims to induce differentiation and apoptosis in malignant cells while managing the potential for myelosuppression, a known risk given MYB's role in normal blood cell development (Ionis Pharmaceuticals, 2020).

Other names

c-Myb mRNAv-myb avian myeloblastosis viral oncogene homolog mRNAProto-oncogene c-Myb mRNAMYB transcript

Antisense oligonucleotide-mediated RNase H-dependent degradation of mRNA