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Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation,
phosphoinositide turnover, and clonal proliferation of human T-lineage
acute lymphoblastic leukemia cells
I Dibirdik, MC Langlie, JA Ledbetter, L Tuel-Ahlgren, V Obuz, KG Waddick, K Gajl-Peczalska, GL Schieven and FM Uckun
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis 55455.
The purposes of this study were to examine the biologic effects of the
engagement of the interleukin-7 receptor (IL-7R) with recombinant human
interleukin-7 (rhIL-7) in immunophenotypically distinct T-lineage acute
lymphoblastic leukemia (ALL) blasts and to elucidate the biochemical nature
of the IL-7R-linked transmembrane signal in rhIL-7-responsive T- lineage
ALL blast populations. In the absence of costimulants, rhIL-7 stimulated
the in vitro proliferation and colony formation of freshly isolated
leukemic blasts from six to eight T-lineage ALL patients with a mean
plating efficiency of 196 +/- 53 (background subtracted) colonies/10(5)
blasts plated. Stimulation of T-lineage ALL blasts with rhIL-7 resulted in
markedly enhanced tyrosine phosphorylation of six distinct phosphoproteins
with molecular weights of 57, 72, 98, 123, 150, and 190 Kd, and induced a
rapid increase in the production of inositol-1,4,5-trisphosphate
(Ins-1,4,5-P3), which was inhibitable by the tyrosine-specific protein
kinase inhibitor genistein, but not by the serine/threonine-specific
protein kinase C inhibitor H7. Similarly, rhIL-7 stimulated Ins-1,4,5-P3
production in CEM-1.3 T-lineage ALL cells and this stimulation was
inhibitable by the tyrosine-specific protein kinase inhibitors genistein
and herbimycin A, but not by H-7. Thus, the transmembrane signal triggered
by engagement of the IL-7R is intimately linked to a functional
tyrosine-specific protein kinase pathway and stimulates the
phosphoinositide (PI) turnover and proliferation of T-lineage ALL blasts.
The presented data confirm and extend previous studies on the expression of
functional IL-7R on T- lineage ALL blasts and support the hypothesis that
IL-7 may play an important regulatory role in the biology of T-lineage ALL.
Volume 78,
Issue 3,
pp. 564-570,
08/01/1991
Copyright © 1991 by The American Society of Hematology
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