PMID- 1650261 OWN - NLM STAT- MEDLINE DCOM- 19910904 LR - 20231120 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 78 IP - 3 DP - 1991 Aug 1 TI - Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation, phosphoinositide turnover, and clonal proliferation of human T-lineage acute lymphoblastic leukemia cells. PG - 564-70 AB - 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. FAU - Dibirdik, I AU - Dibirdik I AD - Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Health Sciences Center, Minneapolis 55455. FAU - Langlie, M C AU - Langlie MC FAU - Ledbetter, J A AU - Ledbetter JA FAU - Tuel-Ahlgren, L AU - Tuel-Ahlgren L FAU - Obuz, V AU - Obuz V FAU - Waddick, K G AU - Waddick KG FAU - Gajl-Peczalska, K AU - Gajl-Peczalska K FAU - Schieven, G L AU - Schieven GL FAU - Uckun, F M AU - Uckun FM LA - eng GR - R01 CA-42633/CA/NCI NIH HHS/United States GR - R01 CA-51425/CA/NCI NIH HHS/United States GR - R29 CA-42111/CA/NCI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cytokines) RN - 0 (Interleukin-7) RN - 0 (Phosphatidylinositols) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Interleukin-7) RN - 0 (Recombinant Proteins) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Bone Marrow/immunology/pathology MH - Cell Division MH - Clone Cells MH - Cytokines/*pharmacology MH - Enzyme Activation MH - Humans MH - Inositol 1,4,5-Trisphosphate/*metabolism MH - Interleukin-7/*pharmacology/physiology MH - Leukemia-Lymphoma, Adult T-Cell/*immunology/pathology MH - Lymphocyte Activation/drug effects MH - Phosphatidylinositols/*metabolism MH - Phosphorylation MH - Protein-Tyrosine Kinases/*metabolism MH - Receptors, Immunologic/*physiology MH - Receptors, Interleukin-7 MH - Recombinant Proteins/pharmacology MH - T-Lymphocytes/drug effects/*immunology EDAT- 1991/08/01 00:00 MHDA- 1991/08/01 00:01 CRDT- 1991/08/01 00:00 PHST- 1991/08/01 00:00 [pubmed] PHST- 1991/08/01 00:01 [medline] PHST- 1991/08/01 00:00 [entrez] AID - S0006-4971(20)85220-3 [pii] PST - ppublish SO - Blood. 1991 Aug 1;78(3):564-70.