Renner Annelies G, Dos Santos Cédric, Recher Christian, Bailly Christian, Créancier Laurent, Kruczynski Anna, Payrastre Bernard, Manenti Stéphane
INSERM Unité 563-IFR30, Centre de Physiopathologie Toulouse-Purpan, Département Oncogenèse et Signalisation dans les cellules hématopoïétiques, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse.
Blood. 2009 Jul 16;114(3):659-62. doi: 10.1182/blood-2008-12-195867. Epub 2009 May 20.
Polo-like kinase 1 (Plk1) is a major mitotic regulator overexpressed in many solid tumors. Its role in hematopoietic malignancies is still poorly characterized. In this study, we demonstrate that Plk1 is highly expressed in leukemic cell lines, and overexpressed in a majority of samples from patients with acute myeloid leukemia compared with normal progenitors. A pharmacologic inhibitor, BI2536, blocks proliferation in established cell lines, and dramatically inhibits the clonogenic potential of leukemic cells from patients. Plk1 knockdown by small interfering RNA also blocked proliferation of leukemic cell lines and the clonogenic potential of primary cells from patients. Interestingly, normal primary hematopoietic progenitors are less sensitive to Plk1 inhibition than leukemic cells, whose proliferation is dramatically decreased by the inhibitor. These results highlight Plk1 as a potentially interesting therapeutic target for the treatment of acute myeloid leukemia.
Polo样激酶1(Plk1)是一种主要的有丝分裂调节因子,在许多实体瘤中过表达。其在血液系统恶性肿瘤中的作用仍未得到充分描述。在本研究中,我们证明Plk1在白血病细胞系中高表达,并且与正常祖细胞相比,在大多数急性髓系白血病患者的样本中过表达。一种药物抑制剂BI2536可阻断已建立细胞系中的增殖,并显著抑制患者白血病细胞的克隆形成潜力。通过小干扰RNA敲低Plk1也可阻断白血病细胞系的增殖以及患者原代细胞的克隆形成潜力。有趣的是,正常原代造血祖细胞对Plk1抑制的敏感性低于白血病细胞,白血病细胞的增殖会被该抑制剂显著降低。这些结果突出了Plk1作为治疗急性髓系白血病潜在的有趣治疗靶点。