Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes from patients with
multiple myeloma
, smoldering
myeloma
or monoclonal gammopathy of undetermined significance. We analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14
+
monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in
myeloma
-enhanced osteoclastogenesis. The number of bone marrow CD14
+
CD16
+
cells was higher in patients with active
myeloma
than in those with smoldering
myeloma
or monoclonal gammopathy of undetermined significance. Interestingly, sorted bone marrow CD14
+
CD16
+
cells from
myeloma
patients were more pro-osteoclastogenic than CD14
+
CD16-cells in cultures
ex vivo
Moreover, transcriptional analysis demonstrated that bone marrow CD14
+
cells from patients with
multiple myeloma
(but neither monoclonal gammopathy of undetermined significance nor smoldering
myeloma
) significantly upregulated genes involved in osteoclast formation, including
IL21R
IL21R
mRNA over-expression by bone marrow CD14
+
cells was independent of the presence of interleukin-21. Consistently, interleukin-21 production by T cells as well as levels of interleukin-21 in the bone marrow were not significantly different among monoclonal gammopathies. Thereafter, we showed that
IL21R
over-expression in CD14
+
cells increased osteoclast formation. Consistently, interleukin-21 receptor signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14
+
cells of
myeloma
patients. Our results indicate that bone marrow monocytes from
multiple myeloma
patients show distinct features compared to those from patients with indolent monoclonal gammopathies, supporting the role of
IL21R
over-expression by bone marrow CD14
+
cells in enhanced osteoclast formation.
...
PMID:
IL21R
expressing CD14
+
CD16
+
monocytes expand in multiple myeloma patients leading to increased osteoclasts. 2805 43
