Researchers at the Leibniz Institute for Immunotherapy (LIT) studied hundreds of patients with acute myeloid leukemia (AML). They discovered that specific mutations in the STAG2 protein cause altered DNA folding in the cell nucleus, thereby contributing to the development of AML. The research is in the journal .
The three-dimensional structure of DNA in the nucleus is stabilized by the cohesin protein complex. It helps to properly fold the DNA and thus regulate . Cohesin contains two very similar subunits, STAG1 or STAG2.
In myeloid leukemias, mutations in the cohesin subunit STAG2 are particularly common, while those in STAG1 are almost never observed. "We wanted to find out why the STAG2 subunit is so often affected and how a mutation leading to the loss of cohesin complex function could contribute to the development of leukemia," explains Prof. Michael Rehli, the head of the LIT research group.
In with Prof. Ruud Delwel of the Erasmus Medical Center in Rotterdam, the researchers examined changes in the spatial DNA structure in AML patient samples with and without cohesin mutations. They found that mutations in STAG2 lead to alterations in the DNA structure in AML cells.
These changes impair normal gene regulation, resulting in certain genes being either overly activated or not activated at all. What is particularly remarkable about this discovery is that these disturbances cannot be compensated for by the STAG1 protein, highlighting the role of STAG2 in AML. In a further s.