Münch Claudia, May Annette M, Hauschke Dieter, Roth Jasmine, Lassmann Silke, Werner Martin
Institute of Pathology, University Medical Center Freiburg, Germany.
Chromosoma. 2011 Jun;120(3):265-73. doi: 10.1007/s00412-011-0309-x. Epub 2011 Feb 1.
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.
巨核细胞生成在骨髓增生异常综合征（MDS）中受到很大干扰，并且巨核细胞（MKs）经常出现多核现象。在此，我们通过连续多位点荧光原位杂交技术研究了7例MDS患者和1例骨髓增生异常/骨髓增殖性肿瘤患者的发育异常的单核、双核和多核MKs（n = 169）。对DNA含量总和为4N的双核MKs（n = 46）进行分析表明，两个独立细胞核之间的染色体分布明显均匀（对称）（p = 0.0223），这表明在第一次核内有丝分裂细胞周期中存在双极纺锤体定向和对称染色体分离。相比之下，更高倍体（>4N，n = 108）的多核MKs在独立细胞核之间表现出明显不均匀（不对称）的染色体分布（p = 0.0248）。因此，发育异常的MKs的核间染色体分布取决于倍体水平。此外，在发育异常的MKs中未发现中心体畸变。我们的结果表明，MDS中的巨核细胞多核化源于失调的核内有丝分裂，包括核分裂的恢复。
