CAR Virus Receptor Mediates Erythroid Differentiation and Migration and is Downregulated in MDS

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2023 Sep 6

PMID 37673973

Authors

Karin Bauer

Sigrid Machherndl-Spandl

Lukas Kazianka

Irina Sadovnik

Sinan Gultekin

Susanne Suessner

Johannes Proell

Jeroen Lauf

Gregor Hoermann

Gregor Eisenwort

Norman Hafner

Mathilde Fodermayr-Mayrleitner

Ann-Sofie Schmolke

Emiel van der Kouwe

Uwe Platzbecker

Thomas Lion

Ansgar Weltermann

Otto Zach

Gerald Webersinke

Ulrich Germing

Christian Gabriel

Wolfgang R Sperr

Marie C Bene

Philipp B Staber

Peter Bettelheim

Peter Valent

Affiliations

Soon will be listed here.

Abstract

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/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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