ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27252013.
- Also identified by DOI 10.1038/ncomms11733 and PMC identifier 4895769.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion.
Medical subject headings
- Core Binding Factor Alpha 2 Subunit
- DNA-Binding Proteins
- Gene Expression Regulation, Leukemic
- Leukemia, Myeloid, Acute
- Mutation
- Oncogene Proteins, Fusion
- RUNX1 Translocation Partner 1 Protein
- Transcription Factors
- Translocation, Genetic