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

Karin BauerSigrid Machherndl-SpandlLukas KaziankaIrina SadovnikSinan GültekinSusanne SuessnerJohannes ProellJeroen LaufGregor HoermannGregor EisenwortNorman HäfnerMathilde Födermayr-MayrleitnerAnn-Sofie SchmolkeEmiel van der KouweUwe PlatzbeckerThomas LionAnsgar WeltermannOtto ZachGerald WebersinkeUlrich GermingChristian GabrielWolfgang R SperrMarie C BénéPhilipp Bernhard StaberPeter BettelheimPeter Valent
Published in: Leukemia (2023)
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.
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