Department of Laboratory Medicine, Kawasaki Medical School, Okayama, Japan.
Leukemia. 2010 Apr;24(4):748-55. doi: 10.1038/leu.2009.296. Epub 2010 Feb 4.
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders characterized by refractory cytopenias and susceptibility to leukemic transformation. On a subset of MDS patients with deletion of the long arm of chromosome 5 (del(5q)), lenalidomide exerts hematological and cytogenetic effects, but the underlying pharmacological mechanisms are not fully understood. In this study, we have investigated the in vitro effects of lenalidomide on an MDS-derived cell line, MDS-L, which carries del(5q) and complex chromosome abnormalities. We found that the growth of MDS-L cells was specifically suppressed mainly by apoptosis, and in addition, multinucleated cells were frequently formed and finally died out in the presence of lenalidomide. Time-lapse microscopic observation and the DNA ploidy analysis revealed that lenalidomide does not affect DNA synthesis but inhibits cytokinesis of MDS-L cells. The gene expression profile showed decreased expression of M phase-related genes such as non-muscle myosin heavy-chain 10, polo-like kinase 1, aurora kinase B, citron kinase and kinesin family member 20A(KIF20A). Interestingly, KIF20A is located at 5q31. These data contribute to the understanding of action mechanisms of lenalidomide on MDS with del(5q) and complex abnormalities.
骨髓增生异常综合征（MDS）是一组造血干细胞疾病，其特征为难治性血细胞减少症和易向白血病转化。在一组伴有 5 号染色体长臂缺失（del(5q)）的 MDS 患者中，来那度胺发挥血液学和细胞遗传学作用，但潜在的药理学机制尚不完全清楚。在这项研究中，我们研究了来那度胺对携带 del(5q)和复杂染色体异常的 MDS 衍生细胞系 MDS-L 的体外作用。我们发现，MDS-L 细胞的生长主要通过凋亡被特异性抑制，此外，在来那度胺存在的情况下，多核细胞经常形成并最终死亡。延时显微镜观察和 DNA 倍性分析显示，来那度胺不影响 DNA 合成，而是抑制 MDS-L 细胞的胞质分裂。基因表达谱显示 M 期相关基因如非肌球蛋白重链 10、 polo 样激酶 1、极光激酶 B、柠檬酸激酶和驱动蛋白家族成员 20A（KIF20A）的表达降低。有趣的是，KIF20A 位于 5q31。这些数据有助于理解来那度胺对具有 del(5q)和复杂异常的 MDS 的作用机制。
