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A model of in vivo cell proliferation of adult T-cell leukemia
A Kondo, K Imada, T Hattori, H Yamabe, T Tanaka, M Miyasaka, M Okuma and T Uchiyama
First Department of Internal Medicine and Laboratory of Anatomic Pathology,
Kyoto University, Japan.
We have made a model of in vivo cell proliferation of leukemic cells from
adult T-cell leukemia (ATL) patients using severe combined immunodeficiency
(SCID) mice. Peripheral blood mononuclear cells (PBMC) or lymph node cells
(LNC) depleted of B cells and monocytes were intraperitoneally injected
into SCID mice treated with antimurine interleukin-2 receptor (IL-2+) beta
chain monoclonal antibody (MoAb)(TM- beta 1), followed by daily injection
of human recombinant IL-2 until 60 days after cell injection. SCID mice
injected with ATL cells from 6 of 8 ATL patients were found to have the
tumor or leukemia 5 to 7 weeks after the inoculation of cells. Serum levels
of soluble form of human IL-2R alpha chain (Tac) were markedly elevated in
such mice. The cells recovered from the mice injected with leukemic cells
from four different ATL patients had the same cell surface phenotype as
that of original leukemic cells which were CD4+Tac+. Furthermore, we
detected the same integration site of human T-cell leukemia virus type I
(HTLV- I) provirus and the same rearrangement pattern of human T-cell
receptor (TCR) beta chain gene as those of ATL cells by Southern blot
hybridization, indicating that the cells proliferating in SCID mice were
derived from the original ATL cell clone. Histologic examination showed
that the pattern of the infiltration of ATL cells into various organs in
SCID mice was similar to that of an ATL patient. Such a model of in vivo
cell proliferation of ATL cells will be useful for the study of the
mechanism of neoplastic cell proliferation and for the development of a new
and effective treatment of ATL.
Volume 82,
Issue 8,
pp. 2501-2509,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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