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99
Kitakanto Med J
2013；63：99∼100
Nelarabine Resistance of Childhood T-Cell
Lymphoblastic Leukemia/Lymphoma Cells
Takashi Kanazawa,
Haruna Okuno,
Tadashi Kumamoto,
Norio Shiba,
Akira Aizawa,
Kazushi Tamura,
Shota Tsukada,
Shiro Yamada,
Yasuko Kobayashi
and Hirokazu Arakawa
Background
Nelarabine (NEL) is a new purine nucleoside
analogue that has recently become available for both
adults and children with relapsed or refractory T-cell
acute lymphoblastic leukemia (T-ALL) and T
-lymphoblastic lymphoma (T-LBL). We studied the
drug resistance profile of eight children with T-ALL/
LBL using an in vitro cytotoxic assay including NEL.
Furthermore, we tried to establish a NEL resistant TALL cell line model to investigate the mechanism of
NEL resistance.
Results
Four of8 patients showed in vitro NEL resistance.
To study the mechanism, we established a nucleoside
analogue resistant T-ALL Jurkat cell line model (Jurkat＋C) by cytarabine (AraC) exposure. Jurkat＋C
showed resistance to NEL and Fludarabine as well as
AraC but not Daunorubicin. Next, we studied the
roleofEquivalent NucleosideTransporter-1(ENT-1),
a major cellular nucleosidetransporter,in theacquired
drug resistance in Jurkat＋C. Nitrobenzylmercaptopurine riboside, an ENT-1-specific inhibitor,
showed an inhibitoryeffect ofnucleosideanalogueson
in vitro toxicity in both Jurkat and Jurkat＋C, while
no differences in ENT -1 mRNA expression levels
between Jurkat and Jurkat＋C were found.
Conclusions
In vitro NEL resistance was seen in half of the
tested childhood T-ALL cells. ENT-1 maypartlyact
as a transporter of NEL, but not play a key role in
AraC induced NEL resistance. This cell line model
maybe useful to provide a mechanism to explain NEL
resistance.
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1 Department ofPediatrics,Gunma UniversityGraduateSchool ofMedicine,3-39-22 Showa-machi,Maebashi,Gunma 371-8511,Japan
2 Department of Pediatrics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
Received : December 13, 2012
Address: TAKASHI KANAZAWA Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan,
100
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