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Myelodysplasias

CD34+ marrow progenitors from MDS patients with high levels of intramedullary apoptosis have reduced expression of α4β1 and α5β1 integrins

Leukemia volume 19, pages 57–63 (2005)Cite this article

Abstract

Excessive intramedullary apoptosis is central in the pathogenesis of myelodysplastic syndromes (MDS). Growth-inhibiting cytokines, the Fas/FasLigand pathway, and autoreactive cytotoxic T-lymphocytes have been identified to be important proapoptotic factors in MDS. In normal hematopoiesis, α4β1 and α5β1 integrin-mediated interactions between progenitors and fibronectin are critical for progenitor cell survival. In this study, we have used flow cytometry to quantify the expression levels of members of the β1 integrin family on CD34+ marrow progenitors in 27 untreated patients with MDS, three with s-AML, and 25 control subjects. In MDS, we observed that nonapoptotic progenitors significantly downregulate cell surface expression levels of α4 and β1 integrin chains compared with healthy controls. Downregulation of α4, β1, and also α5 was present in MDS patients with ≥25% apoptotic progenitors, irrespective of their French, American, British subcategory. Reduced cell surface expression levels of α4, α5, and β1 did also correlate with decreased in vitro adhesiveness to fibronectin fragments. Therefore, our observations suggest that downregulation of α4β1 and α5β1 integrins on CD34+ progenitors could be a newly identified proapoptotic mechanism in MDS.

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Authors and Affiliations

  1. Department of Hematology, University Hospital Leuven, Leuven, Belgium

    M Delforge & M Boogaerts

  2. Laboratory of Experimental Hematology, Catholic University Leuven, Leuven, Belgium

    V Raets & V Van Duppen

  3. Center for Human Genetics, University Hospital Leuven, Leuven, Belgium

    P Vandenberghe

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  1. M Delforge
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  2. V Raets
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  3. V Van Duppen
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  4. P Vandenberghe
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  5. M Boogaerts
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Correspondence to M Delforge.

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Delforge, M., Raets, V., Van Duppen, V. et al. CD34+ marrow progenitors from MDS patients with high levels of intramedullary apoptosis have reduced expression of α4β1 and α5β1 integrins. Leukemia 19, 57–63 (2005). https://doi.org/10.1038/sj.leu.2403551

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