Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets.
The translocation t(8;21), leading to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer.
Altered expression of runt-related transcription factor 1 (RUNX1T1) has been observed in several human cancer types; however, the exact role for RUNX1T1 in colorectal cancer (CRC) remains unclear.
Here, we show that RUNX1-ETO undergoes degradation in response to treatment with histone deacetylase inhibitors, one of which, depsipeptide (DEP), is currently undergoing phase II clinical testing in a variety of malignancies.
The mutation rate of genes other than mismatch repair or p53 is the same in colon cancer and in normal cells, indicating that a 'mutator phenotype', increasing the rate of mutations in many genes, is not an essential feature of sporadic cancers; conversely, fusion genes, TEL-AML1/AML1-ETO, typical of leukemia, are 100 times more frequent at birth than in overt leukemia in children, indicating that further selective events are needed to cause malignancy.
Some recurrent aberrations and the resulting gene rearrangements, namely inv(16)/t(16;16) and CBFbeta- MYH11, t(8;21) and CBFA2-CBFA2T1, t(15;17) and PML-RARalpha, and rearrangements of band 11q23 and the MLL gene, are now used to help define distinct disease entities within AML in the new World Health Organization classification of haematological malignancies.