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Establishment of a human acute promyelocytic leukemia-ascites model in SCID
mice
SY Zhang, J Zhu, GQ Chen, XX Du, LJ Lu, Z Zhang, HJ Zhong, HR Chen, ZY Wang, R Berger, M Lanotte, S Waxman, Z Chen and SJ Chen
Shangai Institute of Materia Medica, Rui-Jin Hospital, China.
Acute promyelocytic leukemia (APL) is an interesting model for cancer
research because of the presence of the specific PML-RARalpha fusion gene
associated with the clinical response to retinoic acid differentiation
therapy. To better understand and improve differentiation induction with
retinoic acid, we have established a human APL-ascites model in SCID mice
using the NB4 human APL cell line. NB4 (1 x 10(6) cells) were transplanted
into the peritoneum (IP) of SCID mice for 1 month. NB4 ascites cells
(A-NB4) appeared, which were then engrafted in SCID mice periodically for
18 passages at an interval of 3 to 4 weeks with a 100% success rate of
tumor induction. The mean survival times of SCID mice transplanted with 1 x
10(6) A-NB4 cells was 21.6 +/- 2.3 days. Analysis of the biologic
characteristics of ninth passage NB4 ascitic cells was performed and they
were found to have the morphologic, immunologic, cytogenetic, and molecular
features of cultured NB4 cells. Furthermore, A-NB4 cells were capable of
differentiating when treated with all-trans retinoic acid (ATRA), as
manifested by enhanced NBT reduction and CD11b expression. In vivo
treatment with ATRA in SCID mice for 4 days also increased NBT reduction by
A-NB4 cells. ATRA treatment significantly prolonged survival time in the
group after transplantation (28.1 +/- 6.8 to 29.1 +/- 8.4 days) compared
with the control (P < .001). Furthermore, treatment with adriamycin, an
effective chemotherapeutic drug in APL, had a strong growth suppressive
effect on A-NB4 cells. These results demonstrate that this SCID-APL (NB4
ascites cells) model is a useful preclinical system for evaluating new or
known drugs in the treatment of APL.
Volume 87,
Issue 8,
pp. 3404-3409,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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