CAR virus receptor mediates erythroid differentiation and migration and is downregulated in MDS.

Autor: Bauer K; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria., Machherndl-Spandl S; Department of Internal Medicine I, Ordensklinikum, Linz, Austria.; Medical Faculty, Johannes Kepler University, Linz, Austria., Kazianka L; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria., Sadovnik I; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria., Gültekin S; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria., Suessner S, Proell J; Medical Faculty, Johannes Kepler University, Linz, Austria.; Department of Molecular Biology, Transfusion Service of Upper Austria, Linz, Austria., Lauf J; Labor Europaplatz, Linz, Austria., Hoermann G; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.; MLL Munich Leukemia Laboratory, Munich, Germany., Eisenwort G; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria., Häfner N; Department of Gynaecology and Obstetrics, Jena University Hospital, Jena, Germany., Födermayr-Mayrleitner M; Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum, Linz, Austria., Schmolke AS; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria., van der Kouwe E; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria., Platzbecker U; Division of Hematology, University of Dresden, Dresden, Germany.; Medical Clinic and Polyclinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany., Lion T; Children´s Cancer Research Institute Vienna und Department of Pediatrics, Medical University of Vienna, Vienna, Austria., Weltermann A; Department of Internal Medicine I, Ordensklinikum, Linz, Austria., Zach O; Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum, Linz, Austria., Webersinke G; Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum, Linz, Austria., Germing U; Department of Hematology, Oncology and Clinical Immunology, Medical University of Düsseldorf, Düsseldorf, Germany., Gabriel C; Department of Molecular Biology, Transfusion Service of Upper Austria, Linz, Austria., Sperr WR; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria., Béné MC; Hematology Laboratory, CHU de Nantes, Nantes, France., Staber PB; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria., Bettelheim P; Labor Europaplatz, Linz, Austria.; Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum, Linz, Austria., Valent P; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. peter.valent@meduniwien.ac.at.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria. peter.valent@meduniwien.ac.at.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2023 Nov; Vol. 37 (11), pp. 2250-2260. Date of Electronic Publication: 2023 Sep 06.
DOI: 10.1038/s41375-023-02015-7
Abstrakt: Myelodysplastic syndromes (MDS) are myeloid neoplasms presenting with dysplasia in the bone marrow (BM) and peripheral cytopenia. In most patients anemia develops. We screened for genes that are expressed abnormally in erythroid progenitor cells (EP) and contribute to the pathogenesis of MDS. We found that the Coxsackie-Adenovirus receptor (CAR = CXADR) is markedly downregulated in CD45 low /CD105 + EP in MDS patients compared to control EP. Correspondingly, the erythroblast cell lines HEL, K562, and KU812 stained negative for CAR. Lentiviral transduction of the full-length CXADR gene into these cells resulted in an increased expression of early erythroid antigens, including CD36, CD71, and glycophorin A. In addition, CXADR-transduction resulted in an increased migration against a serum protein gradient, whereas truncated CXADR variants did not induce expression of erythroid antigens or migration. Furthermore, conditional knock-out of Cxadr in C57BL/6 mice resulted in anemia and erythroid dysplasia. Finally, decreased CAR expression on EP was found to correlate with high-risk MDS and decreased survival. Together, CAR is a functionally relevant marker that is down-regulated on EP in MDS and is of prognostic significance. Decreased CAR expression may contribute to the maturation defect and altered migration of EP and thus their pathologic accumulation in the BM in MDS.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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