The Polo-Like Kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia
CD56 is expressed in 15-20% of acute myeloid leukemia (AML) cases and is linked to extramedullary spread, multidrug resistance, and poor prognosis. In this study, we describe the development and characterization of a novel disseminated model of AML (AML-NS8), created by injecting leukemic blasts freshly isolated from a patient with aggressive CD56(+) monoblastic AML (M5a) into mice. The model successfully reproduced typical features of this leukemia, including extramedullary masses and central nervous system involvement, while maintaining the original phenotype, karyotype, and genotype of the leukemic cells in vivo. Recently, Polo-Like Kinase 1 (PLK1) has emerged as a promising drug target in AML. To assess its potential, we tested the PLK1 inhibitor NMS-P937 in this model, both during engraftment and in established disease stages. In both settings, NMS-P937 showed significant efficacy compared to standard therapies, with a notable increase in median survival time (MST), especially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine, and NMS-P937, respectively). Importantly, we also observed specific biomarker modulation in extramedullary tissues in response to NMS-P937 treatment. This new in vivo model of CD56(+) AML, which closely mirrors the human disease, provides strong support for the therapeutic potential of PLK1 inhibitors in AML.