Researchers from the Tumour Suppression Group at the Spanish National Cancer Research Centre (CNIO), headed by Manuel Serrano, created the first animal model that recapitulates key characteristics of Diamond-Blackfan anaemia (DBA) in humans, including high cancer susceptibility.
The finding could potentially improve current treatments for this disease, which are effective in resolving the haematological disorders but not in preventing the greater predisposition to cancer.
DBA is a rare type of anaemia that affects 5 people per million. It is characterised by blood disorders, short stature and malformations in the heart, palate and hands.
Researchers found that mice with partial deficiency of RPL11 protein (ie one of the two copies of the gene is faulty) not only suffer from the incorrect generation and maturation of red blood cells (causing anaemia), but are also predisposed to lymphomagenesis - the development of lymphomas.
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DBA patients display alterations in ribosomal proteins, those that belong to the ribosomes, the organelles within cells that are responsible for synthesising proteins.
"Cells need the ribosomes to function properly in order to proliferate and grow; we knew that when something goes wrong in these organelles, RPL11 operates as a switch that activates the p53 gene to stop the cells from proliferating and forming tumours; this mechanism is called ribosomal stress," said Serrano.
"P53 is one of the main tumour suppressor genes identified to date, to the extent that its relevance in preventing cancer has led to it being named the guardian of the genome," Serrano said.
"We believe that in DBA both factors combined contribute to induce the development of cancer," said lead author Lucia Morgado-Palacin, from CNIO.
The study was published in the journal Cell Reports.