Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias
C Skjonsberg, BK Erikstein, EB Smeland, SO Lie, S Funderud, K Beiske and HK Blomhoff
Department of Pathology, Norwegian Radium Hospital, Oslo.
The bone marrow stromal cell-derived growth factor interleukin-7 (IL-7) is
known to stimulate growth of normal human B-cell precursors. In the present
report, we have examined the effect of IL-7 on neoplastic B- cell
precursors. Leukemic cells from 20 patients with common acute lymphoblastic
leukemia (ALL) were highly purified by removing contaminating T cells and
monocytes by rosetting with immunomagnetic beads. IL-7 markedly reduced the
DNA synthesis in leukemic cells from three patients. This inhibition of DNA
synthesis was accompanied by maturation of the cells, as demonstrated by
the induced expression of the differentiation antigens CD19, CD20, CDw75,
and surface mu-chain, and a decreased expression of terminal
deoxynucleotidyl transferase. By examining G1 parameters, such as MYC, 4F2,
and transferrin-receptor levels analyzed by flow cytometry as well as RNA
and the cell cycle regulated antigen Ki67, it appeared that the cells were
inhibited late in G1. Leukemic cells from the majority of the cases (12 of
the 20 patients) responded to IL-7 with enhanced DNA synthesis without
detectable maturation, as has been reported for their normal counterparts.
Low molecular weight B-cell growth factor greatly potentiated the
IL-7-induced growth stimulation of these cells. Thus, we have shown that
IL-7 is capable of inhibiting proliferation of leukemic cells isolated from
a subgroup of ALLs, and that this growth inhibition is accompanied by
maturation of the cells.
Volume 77,
Issue 11,
pp. 2445-2450,
06/01/1991
Copyright © 1991 by The American Society of Hematology