Engagement of Interleukin-7 Receptor Stimulates Tyrosine Phosphorylation, Phosphoinositide Turnover, and Clonal Proliferation of Human T-Lineage Acute Lymphoblastic Leukemia Cells

• Published in: Blood 1991-08, Vol.78 (3), p.564-570
• Main Authors: Dibirdik, llker, Langlie, Mridula-Chandan, Ledbetter, Jeffrey A., Tuel-Ahlgren, Lisa, Obuz, Vedat, Waddick, Kevin G., Gajl-Peczalska, Kazimiera, Schieven, Gary L., Uckun, Fatih M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Bone Marrow - immunology; Bone Marrow - pathology; Cell Division; Clone Cells; Cytokines - pharmacology; Enzyme Activation; Hematologic and hematopoietic diseases; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Interleukin-7 - pharmacology; Interleukin-7 - physiology; Leukemia-Lymphoma, Adult T-Cell - immunology; Leukemia-Lymphoma, Adult T-Cell - pathology; Lymphocyte Activation - drug effects; Medical sciences; Phosphatidylinositols - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Receptors, Immunologic - physiology; Receptors, Interleukin-7; Recombinant Proteins - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.3.564.564

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 (rhlL-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 rhlL-7-responsive T-lineage ALL blast populations. In the absence of costimulants, rhlL-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/105 blasts plated. Stimulation of T-lineage ALL blasts with rhlL-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 (lns-1,4,5-P3), which was inhibitable by the tyrosine-specific protein kinase inhibitor genistein, but not by the serine/threonine-specif ic protein kinase C inhibitor H7. Similarly, rhlL-7 stimulated lns-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.