Contributions
Abstract: EP897
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Myelodysplastic syndromes (MDS) are myeloid neoplasms presenting with dysplasia in the bone marrow (BM) and peripheral cytopenia. Most patients present with erythroid hyperplasia in the BM and anemia.
Aims
We screened for genes that are expressed abnormally in erythroid progenitor cells (EryPC) and contribute to the pathogenesis of MDS.
Methods
In mRNA array- and flow cytometry staining experiments, we found that the Coxsackie-Adenovirus receptor (CAR) is markedly downregulated in CD45low/CD105+ EryPC in MDS patients compared to control EryPC.
Results
CAR was also down-regulated in EryPC in patients with acute myeloid leukemia with BM dysplasia. Correspondingly, the erythroblast cell lines HEL, K562, and KU812 stained negative for CAR. Lentiviral transduction of the full-length CAR gene into these cells resulted in an increased expression of early erythroid antigens, including CD36, CD71, and glycophorin A. In addition, CAR-transduction resulted in an increased migration against a serum protein gradient, whereas transfection of truncated CAR-variants did not induce erythroid antigens or migration. Furthermore, we found that conditional knock-out of Car in hematopoietic cells in C57BL/6 mice results in anemia, an accumulation of erythroid cells in the BM, erythroid dysplasia and impaired migration of murine EryPC against a serum protein gradient. Decreased CAR expression on EryPC was found to correlate with high-risk MDS and decreased survival.
Conclusion
Together, CAR is a functionally relevant marker that is down-regulated on EryPC in MDS and is of prognostic significance. Decreased CAR expression may contribute to the maturation defect and altered migration of EryPC and thus their pathologic accumulation in the BM in MDS.
Keyword(s):
Abstract: EP897
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Myelodysplastic syndromes (MDS) are myeloid neoplasms presenting with dysplasia in the bone marrow (BM) and peripheral cytopenia. Most patients present with erythroid hyperplasia in the BM and anemia.
Aims
We screened for genes that are expressed abnormally in erythroid progenitor cells (EryPC) and contribute to the pathogenesis of MDS.
Methods
In mRNA array- and flow cytometry staining experiments, we found that the Coxsackie-Adenovirus receptor (CAR) is markedly downregulated in CD45low/CD105+ EryPC in MDS patients compared to control EryPC.
Results
CAR was also down-regulated in EryPC in patients with acute myeloid leukemia with BM dysplasia. Correspondingly, the erythroblast cell lines HEL, K562, and KU812 stained negative for CAR. Lentiviral transduction of the full-length CAR gene into these cells resulted in an increased expression of early erythroid antigens, including CD36, CD71, and glycophorin A. In addition, CAR-transduction resulted in an increased migration against a serum protein gradient, whereas transfection of truncated CAR-variants did not induce erythroid antigens or migration. Furthermore, we found that conditional knock-out of Car in hematopoietic cells in C57BL/6 mice results in anemia, an accumulation of erythroid cells in the BM, erythroid dysplasia and impaired migration of murine EryPC against a serum protein gradient. Decreased CAR expression on EryPC was found to correlate with high-risk MDS and decreased survival.
Conclusion
Together, CAR is a functionally relevant marker that is down-regulated on EryPC in MDS and is of prognostic significance. Decreased CAR expression may contribute to the maturation defect and altered migration of EryPC and thus their pathologic accumulation in the BM in MDS.
Keyword(s):