The Role of Haploinsufficiency of rps14 and p53 Activation in the Molecular Pathogenesis of the 5q- Syndrome

In recent years we have gained great insight into the molecular pathogenesis of the 5q- syndrome, a distinct subtype of myelodysplasia. The demonstration of haploinsufficiency of the ribosomal gene RPS14 (mapping to the commonly deleted region) and the finding that this is the cause of the erythroid defect in the 5qsyndrome represent major advances. A mouse model of the human 5q- syndrome generated by large-scale deletion of the Cd74-Nid67 interval (containing RPS14) further supports a critical role for RPS14 haploinsufficiency. It is widely accepted that ribosomal deficiency results in p53 activation and defective erythropoiesis and the crossing of the ‘5q- mice’ with p53 deficient mice ameliorated the erythroid progenitor defect. Emerging data suggests that the p53 activation observed in the mouse model may also apply to the human 5q- syndrome.