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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-3-4
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pubmed:abstractText |
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) gene expression is abnormally regulated in multiple myeloma (MM) owing to imbalanced expression of the acute myeloid leukemia-1A (AML-1A) and AML-1B transcription factors. We hypothesized that the increased expression ratios of AML-1A to AML-1B also induced abnormal expression of other hematopoietic and bone-specific genes that contribute to the poor prognosis of MM patients with high levels of MIP-1 alpha. We found that interleukin-3 (IL-3) was also induced by the imbalanced AML-1A and AML-1B expression in myeloma. IL-3 mRNA levels were increased in CD138+ purified myeloma cells with increased AML-1A-to-AML-1B expression from MM patients, and IL-3 protein levels were significantly increased in freshly isolated bone marrow plasma from MM patients (66.4 +/- 12 versus 22.1 +/- 8.2 pg/mL; P = .038). IL-3 in combination with MIP-1 alpha or receptor activator of nuclear factor-kappa B ligand (RANKL) significantly enhanced human osteoclast (OCL) formation and bone resorption compared with MIP-1 alpha or RANKL alone. IL-3 stimulated the growth of interleukin-6 (IL-6)-dependent and IL-6-independent myeloma cells in the absence of IL-6, even though IL-3 did not induce IL-6 expression by myeloma cells. These data suggest that increased IL-3 levels in the bone marrow microenvironment of MM patients with imbalanced AML-1A and AML-1B expression can increase bone destruction and tumor cell growth.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4,
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 2 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RUNX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Activator of Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF11A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2308-15
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14615378-Antibodies,
pubmed-meshheading:14615378-Bone Marrow Cells,
pubmed-meshheading:14615378-Bone Resorption,
pubmed-meshheading:14615378-Carrier Proteins,
pubmed-meshheading:14615378-Cell Differentiation,
pubmed-meshheading:14615378-Cell Division,
pubmed-meshheading:14615378-Cell Line, Tumor,
pubmed-meshheading:14615378-Chemokine CCL4,
pubmed-meshheading:14615378-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:14615378-DNA-Binding Proteins,
pubmed-meshheading:14615378-Down-Regulation,
pubmed-meshheading:14615378-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:14615378-Humans,
pubmed-meshheading:14615378-Interleukin-3,
pubmed-meshheading:14615378-Macrophage Inflammatory Proteins,
pubmed-meshheading:14615378-Membrane Glycoproteins,
pubmed-meshheading:14615378-Multiple Myeloma,
pubmed-meshheading:14615378-Osteoclasts,
pubmed-meshheading:14615378-Proto-Oncogene Proteins,
pubmed-meshheading:14615378-RANK Ligand,
pubmed-meshheading:14615378-RNA, Messenger,
pubmed-meshheading:14615378-Receptor Activator of Nuclear Factor-kappa B,
pubmed-meshheading:14615378-Transcription Factors,
pubmed-meshheading:14615378-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells.
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pubmed:affiliation |
Department of Medicine, Hematology/Oncology Division, University of Pittsburgh, and Department of Vetrerans Affairs Medical Center, PA 15213, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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