Since corepressors participate and regulate a vast range of gene expression, it is not surprising that aberrant corepressor activities can cause diseases.
Acute myeloid leukemia (AML) is a highly lethal blood cancer characterized by uncontrolled myeloid cell growth. Two homologous corepressor genes, BCOR (BCL6 corepressor) and BCORL1, are recurrently mutated in AML patients. BCOR works with multiple transcription factors and is known to play vital regulatory roles in embryonic development. Clinical results detected BCOR somatic mutations in ~4% of an unselected group of AML patients, and ~17% in a subset of patients who lack known AML-causing mutations. Similarly, BCORL1 is a corepressor that regulates cellular processes, and was found to be mutated in ~6% of tested AML patients. These studies point out a strong association between corepressor mutations and AML. Further corepressor research may reveal potential therapeutic targets for AML and other diseases.