Abstract
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.
| Original language | English |
|---|---|
| Article number | 22483 |
| Number of pages | 11 |
| Journal | Scientific Reports |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 18 Nov 2021 |
Bibliographical note
Funding Information:We would like to thank staff at the haematology clinic, Siriraj Hospital for blood sample collections. This study was supported by the National Research Council of Thailand (NRCT) through Mahidol University (R016010007) and the NHS Blood and Transplant (NHSBT) and the NIHR Blood and Transplant Research Unit (NIHR BTRU) in Red Cell Products (IS-BTU-1214-10032). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. C.T. is supported by Siriraj Graduate Scholarships. C. Metheetrairut and KT are supported by Chalermphrakiat Grant, Faculty of Medicine Siriraj Hospital, Mahidol University. Ms Wipada Phromkhunthod, our managerial staff, is supported by Faculty of Medicine Siriraj Hospital.
Publisher Copyright:
© 2021, The Author(s).