A team of researchers led by the Mead Group at the MRC Weatherall Institute of Molecular Medicine (MRC WIMM), alongside Stefan Constantinescu and Bethan Psaila from Ludwig Oxford, have recently published new findings in Nature Genetics.
The study investigates the role of chromothripsis – the rearrangement of genomic material caused by chromosomes breaking apart and reassembling – in blast phase myeloproliferative neoplasm (BP-MPN), a highly aggressive and treatment resistant form of leukaemia.
The researchers 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.
Find out more by reading the full paper here.