B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia : II interleukin-1-mediated autocrine growth regulation of the lymphoblasts
1995
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-1β had a growth-promoting effect on W1 colony numbers when cells were seeded at low density ; W1 cells constitutively expressed mRNA for IL-1β, and high levels of IL-1β were measured in W1 cell lysates ; anti-IL-1β 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-lL-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 exogeneous TNF-a which contrasts sharply with the autocrine growth promoting effect of TNF-α on myelomonocytic elements of JCML in 'chronic' phase. The inhibitory effect of TNF-α 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.
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