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Chromosoma

, Volume 120, Issue 3, pp 265–273 | Cite as

Internuclear chromosome distribution of dysplastic megakaryocytes in myelodysplastic syndromes is dependent on the level of ploidy

  • Claudia Münch
  • Annette M. May
  • Dieter Hauschke
  • Jasmine Roth
  • Silke Lassmann
  • Martin WernerEmail author
Research Article

Abstract

Megakaryopoiesis is largely disturbed in myelodysplastic syndromes (MDS), and megakaryocytes (MKs) frequently show multinucleation. Here, we investigated dysplastic mono-, bi-, and multinuclear MKs (n = 169) of seven patients with MDS and one patient with myelodysplastic/myeloproliferative neoplasm by sequential multilocus FISH. Analysis of binuclear MKs with a combined DNA content of 4 N (n = 46) indicated a significantly even (symmetric) chromosome distribution between the two separate nuclei (p = 0.0223), which suggests bipolar spindle orientation and symmetric chromosome segregation during the first endomitotic cell cycle. In contrast, multinuclear MKs of higher ploidy (>4 N, n = 108) demonstrated a significantly uneven (asymmetric) chromosome distribution between the separate nuclei (p = 0.0248). Thus, the internuclear chromosomal distribution of dysplastic MKs depends on the level of ploidy. In addition, centrosomal aberrations were not found in dysplastic MKs. Our results indicate that megakaryocytic multinucleation in MDS originates from dysregulated endomitosis, including restoration of karyokinesis.

Keywords

Chromosome Distribution Bone Marrow Smear Lobulated Nucleus Chromosome Specific Probe Separate Nucleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We are grateful to Mrs. Inga Sandrock for participating in the study as part of a laboratory internship. FISH probes were generously provided by Dr. M. Rocchi (Bari, Italy). This study was awarded a poster prize at the international meeting “Signal Transduction and Disease 2009” organized by the German, Netherlands, and Belgian Societies of Biochemistry and Molecular Biology. S.L. and M.W. further acknowledge the long-term support by the Mushett Family Foundation (Chester, NJ, US).

Supplementary material

412_2011_309_MOESM1_ESM.doc (30 kb)
Supplementary Table 1 Results of centrosome analysis of MKs in control bone marrow smears (DOC 29 kb)
412_2011_309_Fig5_ESM.gif (86 kb)
Supplementary Figure 1

Centrosome staining of control MKs. Centrosomes were stained with a monoclonal mouse antibody to pericentrin and visualized with AlexaFluor568 goat anti-mouse (red). (A) Control MK with separate centrosomes with cytoplasmic localization. (B) Control MK with centrosome cluster and additional separate centrosomes. (C) Control MK with a centrosome cluster.

412_2011_309_MOESM2_ESM.tif (960 kb)
High Resolution Image File (TIFF 960 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Claudia Münch
    • 1
  • Annette M. May
    • 1
  • Dieter Hauschke
    • 2
  • Jasmine Roth
    • 1
  • Silke Lassmann
    • 1
  • Martin Werner
    • 1
    Email author
  1. 1.Institute of PathologyUniversity Medical Center FreiburgFreiburgGermany
  2. 2.Institute of Medical Biometry and Medical InformaticsUniversity Medical Center FreiburgFreiburgGermany

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