Dussault Nathalie, Simard Carl, Néron Sonia, Côté Serge
Département de Recherche et Développement, Héma-Québec, Québec, PQ, Canada.
Blood Cells Mol Dis. 2007 Jul-Aug;39(1):130-4. doi: 10.1016/j.bcmd.2007.02.010. Epub 2007 Apr 16.
We show that prolonged exposure of non-Hodgkin's lymphoma (NHL) cell lines to low doses of the Src family protein tyrosine kinases (SFKs) inhibitor SU6656 caused proliferation abrogation as a result of the formation of cells with single multilobed nuclei and several mitotic spindle poles, features similar to polyploid megakaryocytes. The propensity of the NHL B cells tested to undergo polyploid was unrelated to the presence of p53 mutations in these cells since comparable outcomes were observed in SU6656-exposed cultures of blood B lymphocytes derived from healthy individuals. Thus, in addition to its utility for the study of megakaryocyte polyploidization, our results show that SU6656 can also induce polyploidy in cells of lymphoid origin, revealing a chemotherapeutic potential for this inhibitor to limit tumor propagation of malignant B cell lymphomas, although not without affecting normal B cells as well.
我们发现，非霍奇金淋巴瘤（NHL）细胞系长时间暴露于低剂量的Src家族蛋白酪氨酸激酶（SFKs）抑制剂SU6656会导致增殖停止，这是由于形成了具有单个多叶核和多个有丝分裂纺锤极的细胞，这些特征类似于多倍体巨核细胞。所测试的NHL B细胞发生多倍体化的倾向与这些细胞中p53突变的存在无关，因为在来自健康个体的血液B淋巴细胞的SU6656处理培养物中观察到了类似的结果。因此，除了其在巨核细胞多倍体化研究中的用途外，我们的结果表明，SU6656还可诱导淋巴来源的细胞发生多倍体化，揭示了这种抑制剂在限制恶性B细胞淋巴瘤肿瘤增殖方面的化疗潜力，尽管它也会影响正常B细胞。
