Linked Life Data

1311195

Source:http://linkedlifedata.com/resource/pubmed/id/1311195

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-3-30
pubmed:abstractText
In previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-alpha Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-alpha Ab and anti-granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM-CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF alpha produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-alpha effect. Expression studies of TNF-alpha and TNF-alpha receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-alpha activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-alpha values. Recombinant interleukin-1 alpha (IL-1 alpha) also stimulated JCML colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-alpha or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-alpha and that the endogenously-produced TNF-alpha and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1 alpha also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF-alpha or both.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:1311195-Base Sequence, pubmed-meshheading:1311195-Bone Marrow, pubmed-meshheading:1311195-Child, pubmed-meshheading:1311195-Child, Preschool, pubmed-meshheading:1311195-Colony-Forming Units Assay, pubmed-meshheading:1311195-Female, pubmed-meshheading:1311195-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:1311195-Hematopoiesis, pubmed-meshheading:1311195-Humans, pubmed-meshheading:1311195-Infant, pubmed-meshheading:1311195-Interleukin-1, pubmed-meshheading:1311195-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:1311195-Male, pubmed-meshheading:1311195-Molecular Sequence Data, pubmed-meshheading:1311195-Receptors, Cell Surface, pubmed-meshheading:1311195-Receptors, Tumor Necrosis Factor, pubmed-meshheading:1311195-Recombinant Proteins, pubmed-meshheading:1311195-Tumor Cells, Cultured, pubmed-meshheading:1311195-Tumor Necrosis Factor-alpha
pubmed:year
1992
pubmed:articleTitle
Central role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia.
pubmed:affiliation
Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't