A team of researchers, led by the Mead Group at the MRC Weatherall Institute of Molecular Medicine, including Stefan Constantinescu and Bethan Psaila from Ludwig Oxford, have published new findings which could pave the way towards treatment for a specific type of leukaemia called blast phase myeloproliferative neoplasm (BP-MPN).
The study investigates the role of chromothripsis – the rearrangement of genomic material caused by chromosomes breaking apart and reassembling – in BP-MPN, a highly aggressive and treatment-resistant form of leukaemia.
In their research, the team found that in their cohort of 64 patients, approximately 25% carried an abnormal gain of genetic material from chromosome 21, known as chr.21amp, with a third of these cases caused by chromothripsis.
Within the amplified region of chromosome 21 the authors identified DYRK1A, a gene involved in the suppression of DNA repair and increased cell survival through upregulation of BCL2, as being consistently over expressed. Importantly, they found that its overexpression was associated with poorer overall survival in patients. By blocking the activity of DYRK1A in model systems, either by switching off the gene or through pharmacological inhibition, the researchers were able to inhibit cancer cell growth.
Taken together, this work highlights the potential of DYRK1A as a possible therapeutic target for BP-MPN.
Find out more by reading the full paper on the Nature Genetics website: https://www.nature.com/articles/s41588-025-02190-6