B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts.
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.
Attias
D
D
Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada.
Grunberger
T
T
Vanek
W
W
Estrov
Z
Z
Cohen
A
A
Lau
R
R
Freedman
M H
MH
D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001752:Blast Crisis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018121:Receptors, Cytokine / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D018121:Receptors, Cytokine; D017472:Receptors, Interleukin-1