骨髓增殖异常综合征（MDS）是以骨髓和外周细胞减少为特征的骨髓系祖细胞肿瘤。大多数患者会出现贫血。我们对在红细胞前体细胞（EP）中异常表达的基因进行了筛选，以确定其对MDS发病机制的贡献。我们发现，考萨奇-腺病毒受体（CAR=CXADR）在MDS患者的CD45low/CD105+ EP中明显下调，与对照组EP相比。相应地，红细胞生长印迹HEL、K562和KU812细胞对CAR的染色呈阴性。将完整的CXADR基因通过慢病毒转导到这些细胞中，导致早期红细胞抗原（包括CD36、CD71和血型糖蛋白A）的表达增加。此外，CXADR转导导致细胞对血清蛋白梯度的迁移增加，而截短型CXADR变体则不会诱导红细胞抗原的表达或迁移。此外，Cxadr的条件性敲除在C57BL/6小鼠中导致贫血和红细胞发育异常。最后，发现EP上CAR的表达降低与高危MDS和生存率降低相关。因此，CAR是一个功能相关的标记，其在MDS中的EP上被下调，并具有预后意义。CAR表达的降低可能导致EP成熟缺陷和迁移异常，进而导致它们在MDS的骨髓中病理性积累。© 2023年。作者（及授权方）专属授权给Springer Nature Limited。

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 CD45low/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.