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Myelodysplasias

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

Leukemia volume 23, pages 886–891 (2009)Cite this article

Abstract

Recent studies in erythroid cells have shown that autophagy is an important process for the physiological clearance of mitochondria during terminal differentiation. However, autophagy also plays an important role in removing damaged and dysfunctional mitochondria. Defective mitochondria and impaired erythroid maturation are important characteristics of low-risk myelodysplasia. In this study we therefore questioned whether the autophagic clearance of mitochondria might be altered in erythroblasts from patients with refractory anemia (RA, n=3) and RA with ringed sideroblasts (RARS, n=6). Ultrastructurally, abnormal and iron-laden mitochondria were abundant, especially in RARS patients. A large proportion (52±16%) of immature and mature myelodysplastic syndrome (MDS) erythroblasts contained cytoplasmic vacuoles, partly double membraned and positive for lysosomal marker LAMP-2 and mitochondrial markers, findings compatible with autophagic removal of dysfunctional mitochondria. In healthy controls only mature erythroblasts comprised these vacuoles (12±3%). These findings were confirmed morphometrically showing an increased vacuolar surface in MDS erythroblasts compared to controls (P<0.0001). In summary, these data indicate that MDS erythroblasts show features of enhanced autophagy at an earlier stage of erythroid differentiation than in normal controls. The enhanced autophagy might be a cell protective mechanism to remove defective iron-laden mitochondria.

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Acknowledgements

We thank Mr I Stokroos for performing the cytomorphometric studies. Dr KN Faber biochemist at the Department of Gastroenterology and Hepatology, University Medical Center Groningen, and Dr AR Bellu, Professor IJ van der Klei and Professor M Veenhuis from the Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, The Netherlands, are thanked for their critical revision of the results. We are grateful to Dr E van den Berg, MD, for performing cytogenetic studies. Mr D Huizinga and Mr BFA Hellinga are thanked for photographical assistance. Financial support was provided by a grant from the JK de Cock Stichting and the Dutch Cancer Foundation (2003–2920). Financial support was provided by a grant from the JK de Cock Stichting and the Dutch Cancer Foundation (2003–2920).

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Authors and Affiliations

  1. Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands

    E J Houwerzijl, H-Wd Pol, N R Blom, JThM de Wolf & E Vellenga

  2. Department of Cell Biology, Molecular Imaging and Electron Microscopy, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands

    N R Blom & J J L van der Want

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  1. E J Houwerzijl
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  2. H-Wd Pol
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Correspondence to E J Houwerzijl.

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Houwerzijl, E., Pol, HW., Blom, N. et al. Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria. Leukemia 23, 886–891 (2009). https://doi.org/10.1038/leu.2008.389

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