Internuclear chromosome distribution of dysplastic megakaryocytes in myelodysplastic syndromes is dependent on the level of ploidy
- 183 Downloads
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.
KeywordsChromosome Distribution Bone Marrow Smear Lobulated Nucleus Chromosome Specific Probe Separate Nucleus
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).
- Roy L, Coullin P, Vitrat N, Hellio R, Debili N, Weinstein J, Bernheim A, Vainchenker W (2001) Asymmetrical segregation of chromosomes with a normal metaphase/anaphase checkpoint in polyploid megakaryocytes. Blood 97:2238–2247Google Scholar
- Schneider M, Lu W, Neumann S et al (2010) Molecular mechanisms of centrosome and cytoskeleton anchorage at the nuclear envelope. Cell Mol Life Sci (in press)Google Scholar
- Shaffer LG, Tommerup N (eds) (2005) ISCN (2005): An international system for human cytogenetic nomenclatureGoogle Scholar
- Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SH, Stein H, Thiele J, Vardiman JW (eds) (2008) World Health Organization Classification of Tumours of haematopoietic and lymphoid tissues. WHO Press, GeneveGoogle Scholar
- Walch A, Bink K, Hutzler P, Bowering K, Letsiou I, Zitzelsberger H, Braselmann H, Stein H, Hofler H, Werner M (2001) Sequential multilocus fluorescence in situ hybridization can detect complex patterns of increased gene dosage at the single cell level in tissue sections. Lab Invest 81:1457–1459PubMedGoogle Scholar
- Yan J, Zhang XX, Fetni R, Drouin R (2001) Trisomy 8 and monosomy 7 detected in bone marrow using primed in situ labeling, fluorescence in situ hybridization, and conventional cytogenetic analyses. A study of 54 cases with hematological disorders. Cancer Genet Cytogenet 125:30–40PubMedCrossRefGoogle Scholar