NI-1: a novel canine mastocytoma model for studying drug resistance and IgER-dependent mast cell activation.

Allergy
Emir HadzijusufovicPeter Valent

Abstract

Advanced mast cell (MC) disorders are characterized by uncontrolled growth of neoplastic MC in various organs, mediator-related symptoms, and a poor prognosis. Kit mutations supposedly contribute to abnormal growth and drug resistance in these patients. We established a novel canine mastocytoma cell line, NI-1, from a patient suffering from MC leukemia. NI-1 cells were found to form mastocytoma lesions in NOD/SCID IL-2Rgamma(null) mice and to harbor several homozygous Kit mutations, including missense mutations at nucleotides 107(C→T) and 1187(A→G), a 12-bp duplication (nucleotide 1263), and a 12-bp deletion (nucleotide 1550). NI-1 cells expressed several MC differentiation antigens, including tryptase, Kit, and a functional IgE receptor. Compared to the C2 mastocytoma cell line harboring a Kit exon 11 mutation, NI-1 cells were found to be less responsive against the Kit tyrosine kinase inhibitors (TKI) masitinib and imatinib, but were even more sensitive against proliferation-inhibitory effects of the mammalian target of rapamycin (mTOR) blocker RAD001 and PI3-kinase/mTOR blocker NVP-BEZ235. The Kit-targeting multikinase inhibitors PKC412 and dasatinib were also found to override TKI resistance in NI-1 cells, and produced grow...Continue Reading

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Citations

Jan 11, 2014·Critical Reviews in Oncology/hematology·Ilaria MarechGirolamo Ranieri
Dec 4, 2014·Critical Reviews in Oncology/hematology·Girolamo RanieriRaffaele Luigi Sciorsci
Aug 11, 2016·Veterinary and Comparative Oncology·K BauerM Willmann
Apr 12, 2017·Veterinary and Comparative Oncology·Alexandra KellerEmir Hadzijusufovic
Aug 24, 2018·Veterinary and Comparative Oncology·Michael WillmannPeter Valent
Oct 3, 2018·The Journal of Pharmacology and Experimental Therapeutics·Eleonora ZorzanMauro Dacasto
Jul 10, 2019·Veterinary and Comparative Oncology·Susanne GamperlEmir Hadzijusufovic
Jun 22, 2018·Journal of Hematology & Oncology·Federico RossariEnrico Orciuolo
Oct 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paulina SobierajskaRafal J Wiglusz

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Methods Mentioned

BETA
flow cytometry
FCS
xenografting
electrophoresis
electron microscopy

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