B-LINEAGE LYMPHOID BLAST CRISIS IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA .2. INTERLEUKIN-1-MEDIATED AUTOCRINE GROWTH-REGULATION OF THE LYMPHOBLASTS

A pre-B acute lymphoblastic leukemia (ALL) cell line with monosomy 7 w as 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 au tocrine pattern of cell proliferation with the following features: W1 colony growth without added growth factor was density-dependent and co lony growth was augmented with serum-free autologous cell culture supe rnatant; exogenous IL-1 beta had a growth-promoting effect on W1 colon y numbers when cells were seeded at low density; W1 cells constitutive ly expressed mRNA for IL-1 beta, and high levels of IL-1 beta were mea sured in W1 cell lysates; anti-IL-1 beta antibodies as well as IL-1 re ceptor antagonist markedly suppressed W1 colony growth when either was added to cultures of cells seeded without growth factors at low densi ty; anti-GM-CSF antibodies and anti-IL-3 antibodies had no inhibitory effect on W1 colony growth. Whereas W1 colony growth was also augmente d by adding IL-3, IL-4, IL-6, IL-7, GM-CSF, Steel factor and erythropo ietin individually to the cultures, W1 cells did not constitutively ex press mRNA for any of these cytokines. W1 colony growth was markedly s uppressed by exogeneous TNF-alpha which contrasts sharply with the aut ocrine 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-depen dent growth of W1 cells appeared to be unique because none of five oth er pre-B lineage ALL cell lines established as controls showed an auto crine 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 receptor s, and IL-1 mediated autocrine cell growth in cancer.