MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera

• Main Authors: Chartsiam Tipgomut, Archrob Khuhapinant, Marieangela C. Wilson, Saiphon Poldee, Kate J. Heesom, Chanatip Metheetrairut, Orapan Sripichai, Chalermchai Mitrpant, Jan Frayne, Kongtana Trakarnsanga
• Other Authors: Siriraj Hospital
• Format: Article
• Published: 2022
• Subjects: Multidisciplinary
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/79194
• Institution: Mahidol University

Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5′-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients’ erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.