The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

Casolaro, A. et al. (2013) The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia. PLoS ONE, 8(3), e58424. (doi: 10.1371/journal.pone.0058424) (PMID:23520509) (PMCID:PMC3592825)

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Abstract

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marchesi, Dr Francesco
Authors: Casolaro, A., Golay, J., Albanese, C., Ceruti, R., Patton, V., Cribioli, S., Pezzoni, A., Losa, M., Texido, G., Giussani, U., Marchesi, F., Amboldi, N., Valsasina, B., Bungaro, S., Cazzaniga, G., Rambaldi, A., Introna, M., Pesenti, E., and Alzani, R.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(3):e58424
Publisher Policy:Reproduced under a Creative Commons License

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