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 language | English (US) |
|---|---|
| Pages (from-to) | 2308-2315 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 103 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2004 |
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ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells
AU - Lee, Jun Won
AU - Chung, Ho Yeon
AU - Ehrlich, Lori A.
AU - Jelinek, Diane F
AU - Callander, Natalie S.
AU - Roodman, G. David
AU - Choi, Sun Jin
PY - 2004/3/15
Y1 - 2004/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1542313900&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542313900&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-06-1992
DO - 10.1182/blood-2003-06-1992
M3 - Article
C2 - 14615378
AN - SCOPUS:1542313900
VL - 103
SP - 2308
EP - 2315
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -