IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells

Jun Won Lee, Ho Yeon Chung, Lori A. Ehrlich, Diane F Jelinek, Natalie S. Callander, G. David Roodman, Sun Jin Choi

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Abstract

Macrophage inflammatory protein-1α (MIP-1α) 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-1α. 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-1α or receptor activator of nuclear factor-kappa B ligand (RANKL) significantly enhanced human osteoclast (OCL) formation and bone resorption compared with MIP-1α 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.

Original languageEnglish (US)
Pages (from-to)2308-2315
Number of pages8
JournalBlood
Volume103
Issue number6
DOIs
StatePublished - Mar 15 2004

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Interleukin-3
Osteoclasts
Macrophage Inflammatory Proteins
Multiple Myeloma
Acute Myeloid Leukemia
Bone
Growth
Interleukin-6
RANK Ligand
Bone Marrow
Bone and Bones
Cell growth
Bone Resorption
Gene expression
Tumors
Transcription Factors
Genes
Plasmas
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Hematology

Cite this

Lee, J. W., Chung, H. Y., Ehrlich, L. A., Jelinek, D. F., Callander, N. S., Roodman, G. D., & Choi, S. J. (2004). IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood, 103(6), 2308-2315. https://doi.org/10.1182/blood-2003-06-1992

IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. / Lee, Jun Won; Chung, Ho Yeon; Ehrlich, Lori A.; Jelinek, Diane F; Callander, Natalie S.; Roodman, G. David; Choi, Sun Jin.

In: Blood, Vol. 103, No. 6, 15.03.2004, p. 2308-2315.

Research output: Contribution to journalArticle

Lee, JW, Chung, HY, Ehrlich, LA, Jelinek, DF, Callander, NS, Roodman, GD & Choi, SJ 2004, 'IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells', Blood, vol. 103, no. 6, pp. 2308-2315. https://doi.org/10.1182/blood-2003-06-1992
Lee, Jun Won ; Chung, Ho Yeon ; Ehrlich, Lori A. ; Jelinek, Diane F ; Callander, Natalie S. ; Roodman, G. David ; Choi, Sun Jin. / IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. In: Blood. 2004 ; Vol. 103, No. 6. pp. 2308-2315.
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AU - Roodman, G. David

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