ETNK1 mutations in atypical chronic myeloid leukaemia can be reverted with phosphoethanolamine

Dr Diletta Fontana - The University of Milano-Bicocca, Milan, Italy

The aim of the study was the characterisation of the role of mutated ETNK1 in the onset of typical chronic myeloid leukaemia that is a clonal disorder that belongs to the group of the myelodysplastic myeloproliferative disorder. The prognosis is very poor and no established standards of care exist for the treatment.

We created different cell lines using the CRISPR-Cas9 technology or using overexpression models. But those used patient samples derived from an ETNK1 positive ACML patient.

We found that in the presence of an ETNK1 mutation there is increasing activity of the mitochondria which ends in the activity of the ROS production. Since ROS are responsible for DNA oxidative damage which occurs in our cellular model as well as in patient samples, there is an increase in DNA damage. We found that there is a significant increase in both the point mutations and DNA double strand breaks.

We found that these findings are due to the absence of the limiting presence of phosphoethanolamine in the cells so we started treating the cells with the phosphoethanolamine which is the product of ETNK1. We were able to revert the phenotype. So we obtained a decrease in the mitochondrial activity, a reduction in the ROS level, and so we were able to block and prevent the accumulation of further mutations in the cells.