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M Eder, OG Ottmann, TE Hansen-Hagge, CR Bartram, S Falk, S Gillis, D Hoelzer and A Ganser
Department of Hematology, University of Frankfurt, Germany.
We investigated the effects of interleukin-3 (IL-3), IL-7, IL-1, and IL- 6,
of irradiated bone marrow-derived fibroblasts (Fb) and of in vitro matured
peripheral blood macrophages (M phi), on the survival, proliferation, and
maturation of purified blasts from nine common acute lymphoblastic
leukemias (cALLs) in 7-day suspension culture. Exposure to IL-3, IL-7,
IL-1, and IL-6 resulted in a mean 2.8-, 1.5-, 1.4-, and 1.6-fold
stimulation of 3H-thymidine (3H-TdR) incorporation, respectively.
Cocultures of cALL blasts with irradiated M phi, either allowing direct
cell-cell contact or preventing it by membrane filters, or with irradiated
Fb, resulted in a mean 31.7-, 4.1-, and 11.2-fold increase of 3H-TdR
incorporation, respectively. Southern blot analysis of immunoglobulin and
T-cell receptor (TCR) gene rearrangements before and after culture
indicated exclusive proliferation of the leukemic clone in three of eight
samples, whereas additional generation of nonleukemic cells was found in
five samples. Polyclonal growth pattern corresponded to the detection of
heterogeneous cell populations using FACS analysis. Survival of cALL blasts
as defined by the detection of cells coexpressing both CD10 and CD19 after
culture was supported by accessory cells in five of eight samples. No
evidence of induced lymphoid maturation was found under any culture
condition. Our data demonstrate supportive effects of stromal cells on cALL
growth, which cannot be replaced by IL-3 or IL-7.
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