Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line.
A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation.
Cohen
A
A
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Grunberger
T
T
Vanek
W
W
Dube
I D
ID
Doherty
P J
PJ
Letarte
M
M
Roifman
C
C
Freedman
M H
MH
D000208:Acute Disease; D000293:Adolescent; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D004247:DNA / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000032:analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D020395:Receptors, Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D009841:Oligonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D020395:Receptors, Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D004247:DNA