Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France.
Leuk Res. 2010 Oct;34(10):1383-9. doi: 10.1016/j.leukres.2009.12.021. Epub 2010 Jan 22.
The polyamine transport system (PTS), hyperactive in cancer cells, can constitute a gate to deliver F14512, a novel spermine epipodophyllotoxin conjugate recently selected for clinical development in AML phase I. We investigated in vitro the high antiproliferative effect of F14512 against 13 leukemia cell lines, and demonstrated a statistically significant correlation with the level of PTS activity, using a novel fluorescent marker F96982. This labelling protocol was then adapted for clinical applications for blood, bone marrow and AML samples with CD45 gating. Within the patient samples, the PTS activity varied significantly in AML cells, as compared to normal lymphocytes. In conclusion, the identification of PTS-positive AML with F98982 probe offers new perspectives to select patients prone to respond to F14512.
多胺转运系统（PTS）在癌细胞中过度活跃，可作为一种门控，将新型精脒表鬼臼毒素缀合物 F14512 递送至 AML 一期临床试验中。我们研究了 F14512 对 13 种白血病细胞系的高抗增殖作用，并使用新型荧光标记物 F96982 证明了与 PTS 活性水平的统计学显著相关性。然后，该标记方案被改编为用于血液、骨髓和 AML 样本（带有 CD45 门控）的临床应用。在患者样本中，与正常淋巴细胞相比，AML 细胞中的 PTS 活性变化显著。总之，使用 F98982 探针鉴定 PTS 阳性 AML 为筛选易对 F14512 产生反应的患者提供了新的视角。
