Leukemic B-Cell Precursors Constitutively Express Functional Receptors for Human Interleukin-1

• Published in: Blood 1989-08, Vol.74 (2), p.761-776
• Main Authors: Uckun, Fatih M., Myers, Dorothea E., Fauci, Anthony S., Chandan-Langlie, Mridula, Ambrus, Julian L.
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - classification; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; Burkitt Lymphoma - immunology; Burkitt Lymphoma - metabolism; Burkitt Lymphoma - pathology; Cell Separation; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Interleukin-1 - metabolism; Interleukin-1 - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Medical sciences; Neoplastic Stem Cells - classification; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Phenotype; Receptors, Immunologic - analysis; Receptors, Immunologic - physiology; Receptors, Interleukin-1; Recombinant Proteins - pharmacology; Tumor Stem Cell Assay
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V74.2.761.761

This study analyzes the expression of functional interleukin-1 (IL-1) receptors on leukemic B-cell precursors (BCPs) from B-cell precursor acute lymphoblastic leukemia (BCP ALL) patients. We first investigated the specific binding of 125Mabeled recombinant IL-1 (125l-rlL-1) (4 × 1017cpm/mol) to fresh marrow blasts from 11 BCP ALL patients. In five of 11 cases, the binding of 125l-rlL-1 was significantly blocked by excess cold rlL-1. In these five cases, the cell-bound radioactivity ranged from 146 cpm/106 cells to 2,412 cpm/106 cells (mean ± SE = 782 ±414 cpm/106 cells), indicating that 4 to 60 femtomols (mean ± SE = 20 ± 10 femtomols) of 126l-rlL-1 were specifically bound per 107 cells. The estimated number of 125l-rlL-1 molecules bound per cell ranged from 219 to 3,618 (mean ± SE = 1173 ± 621). In all five cases, BCP colony formation was stimulated by 10 ng/mL (570 femtomolar) rlL-1, and the background-subtracted colony numbers ranged from 130 to 298 (mean ± SE - 226 ± 31). In contrast, no stimulation was observed in six cases that showed no significant 125l-rlL-1 binding. Hence, there was a high correlation between 125l-rlL-1 binding and IL-1 responsiveness, indicating that functional IL-1 receptors were detected in ligand binding assays. Scatchard plot analysis of the specific equilibrium binding data for leukemic BCPs from two IL-1-responsive BCP ALL cases yielded straight linear regression lines, indicating the existence of a single class of 132 to 154 high affinity IL-1 receptors/cell. The apparent affinity constants (Ka) values ranged from 5.2 × 109 mol/L-1 to 1.2 × 1010 mol/L“1. Notably, the concentrations of IL-1 required for half-maximal receptor occupancy (kd = 83 pmol/L to 190 pmol/L) were approximately three orders of magnitude higher than those needed to elicit a half-maximal proliferative response of leukemic BCPs in colony assays (0.1 to 1.0 ng/mL = 5.7 to 57 femtomolar), indicating that only a small fraction of IL-1 receptors need to be occupied to stimulate leukemic BCPs. Notably, IL-1 unresponsive leukemic BCPs from one BCP ALL patient and two BCP ALL cell lines (REH, KM-3) did not exhibit any significant IL-1 binding (