Leukemic mutation

A genetic mutation that disrupts the exchange of DNA information with the rest of the cell is associated with a large number of cases of blood tumors. Thanks to the collaboration between biologists from the Cold Spring Harbor Laboratory (CSHL) and oncologists from Memorial Sloan-Kettering Cancer Center (MSKCC), it became known how one mutation triggers a chain of biological events leading to most types of leukemia.

The fatal chain of events begins with the splicing of matrix RNA, a process that converts messages from DNA into instructions for creating proteins in the cell. Mistakes in splicing can lead to the synthesis of incorrect proteins that are unable to do their job. The group found that in leukemia, the process associated with splicing, the so-called nonsense-mediated mRNA decay (NMD) is overly active. After splicing converts DNA messages, the NMD process usually serves as a "quality control", destroying error messages before protein synthesis begins.

The researchers determined that when the SRSF2 gene mutates, NMD destroys many more messages, including those that were not previously likely targets of NMD messages, which are important for the production of healthy proteins. As a result of overactive NMD, less healthy and defective or immature blood cells appear – a sign of leukemia.

Mutations of the RNA splicing factor are observed in almost all forms of blood oncopathology, both in chronic and acute myeloid leukemia, as well as even in chronic lymphocytic leukemia.

Previously, scientists have discovered how other cancers manipulate NMD to protect solid tumors. However, the new study is the first evidence that NMD contributes to the appearance of blood tumors.

In order to prevent the mutated SRSF2 gene from affecting NMD, the researchers experimented with the technique of antisense oligonucleotide therapy (ASA). This method has previously shown effectiveness in the fight against diseases resulting from defective RNA splicing. The next step will be to test ASO in animals and refine the approach until it is ready for clinical use.

Article by M.A.Rahman et al. Recurrent SRSF2 mutations in MDS affect both splicing and NMD is published in the journal Genes and Development.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of CSHL: Mutation's role in blood cancers revealed by ideal team-up.