The Polo-Like Kinase 1 (PLK1) Inhibitor NMS-P937 Is Effective in a New Model of Disseminated Primary CD56+ Acute Monoblastic Leukaemia

被引：31

作者：

Casolaro, Alessia ^{[1
]}

Golay, Josee ^{[2
]}

Albanese, Clara ^{[1
]}

Ceruti, Roberta ^{[1
]}

Patton, Veronica ^{[1
]}

Cribioli, Sabrina ^{[1
]}

Pezzoni, Alice ^{[3
]}

Losa, Marco ^{[4
]}

Texido, Gemma ^{[1
]}

Giussani, Ursula ^{[5
]}

Marchesi, Francesco ^{[6
]}

Amboldi, Nadia ^{[1
]}

Valsasina, Barbara ^{[1
]}

Bungaro, Silvia ^{[7
]}

Cazzaniga, Gianni ^{[7
]}

Rambaldi, Alessandro ^{[2
]}

Introna, Martino ^{[2
]}

Pesenti, Enrico ^{[1
]}

Alzani, Rachele ^{[1
]}

机构：

[1] Nerviano Med Sci, Milan, Italy

[2] Osped Riuniti Bergamo, Lab Cellular Therapy G Lanzani, USC Haematol, I-24100 Bergamo, Italy

[3] Ist Clin Humanitas, Dept Haematol & Oncol, Milan, Italy

[4] Fdn Filarete, Milan, Italy

[5] Osped Riuniti Bergamo, Dept Med Genet, I-24100 Bergamo, Italy

[6] Accelera Srl, Milan, Italy

[7] Univ Milano Bicocca, Pediat Clin, Tettamanti Res Ctr, Monza, Italy

来源：

PLOS ONE | 2013年 / 8卷 / 03期

关键词：

ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; COPY-NUMBER ALTERATIONS; IN-VIVO; XENOGRAFT MODELS; SCID MICE; EXPRESSION; MOUSE; CELLS; AML;

D O I：

10.1371/journal.pone.0058424

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 38 条

[1] End points to establish the efficacy of new agents in the treatment of acute leukemia [J].