B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts

Leukemia. 1995 May;9(5):884-8.

Abstract

A pre-B acute lymphoblastic leukemia (ALL) cell line with monosomy 7 was established from a child with juvenile chronic myelogenous leukemia (JCML) in lymphoid blast crisis. Analysis of the growth properties of the cell line, termed 'W1' showed an interleukin-1 (IL-1) mediated autocrine pattern of cell proliferation with the following features: W1 colony growth without added growth factor was density-dependent and colony growth was augmented with serum-free autologous cell culture supernatant; exogenous IL-1 beta had a growth-promoting effect on W1 colony numbers when cells were seeded at low density; W1 cells constitutively expressed mRNA for IL-1 beta, and high levels of IL-1 beta were measured in W1 cell lysates; anti-IL-1 beta antibodies as well as IL-1 receptor antagonist markedly suppressed W1 colony growth when either was added to cultures of cells seeded without growth factors at low density; anti-GM-CSF antibodies and anti-IL-3 antibodies had no inhibitory effect on W1 colony growth. Whereas W1 colony growth was also augmented by adding IL-3, IL-4, IL-6, IL-7, GM-CSF, Steel factor and erythropoietin individually to the cultures, W1 cells did not constitutively express mRNA for any of these cytokines. W1 colony growth was markedly suppressed by exogenous TNF-alpha which contrasts sharply with the autocrine growth promoting effect of TNF-alpha on myelomonocytic elements of JCML in 'chronic' phase. The inhibitory effect of TNF-alpha on W1 cells was not due to downregulation of IL-1 production. The IL-1-dependent growth of W1 cells appeared to be unique because none of five other pre-B lineage ALL cell lines established as controls showed an autocrine growth loop via IL-1. W1 cells provide a valuable opportunity to examine the relationship of monosomy 7, B-lineage acute lymphoblastic leukemia, aberrant genetic expression of cytokines and their receptors, and IL-1 mediated autocrine cell growth in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Blast Crisis*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Child
  • Cytokines / genetics
  • Cytokines / pharmacology
  • Gene Expression
  • Growth Substances / biosynthesis
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / physiology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Receptors, Cytokine / genetics
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / genetics
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Growth Substances
  • Interleukin-1
  • Receptors, Cytokine
  • Receptors, Interleukin-1