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2017 ; 8
(34
): 56598-56611
Nephropedia Template TP
gab.com Text
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English Wikipedia
Expression of CD38 in myeloma bone niche: A rational basis for the use of
anti-CD38 immunotherapy to inhibit osteoclast formation
#MMPMID28915615
Costa F
; Toscani D
; Chillemi A
; Quarona V
; Bolzoni M
; Marchica V
; Vescovini R
; Mancini C
; Martella E
; Campanini N
; Schifano C
; Bonomini S
; Accardi F
; Horenstein AL
; Aversa F
; Malavasi F
; Giuliani N
Oncotarget
2017[Aug]; 8
(34
): 56598-56611
PMID28915615
show ga
It is known that multiple myeloma (MM) cells express CD38 and that a recently
developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma
killing. However, the expression of CD38 and other functionally related
ectoenzymes within the MM bone niche and the potential effects of Daratumumab on
bone cells are still unknown. This study firstly defines by flow cytometry and
immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of
patients with MM and indolent monoclonal gammopathies. Results indicate that only
plasma cells expressed CD38 at high level within the bone niche. In addition, the
flow cytometry analysis shows that CD38 was also expressed by monocytes and early
osteoclast progenitors but not by osteoblasts and mature osteoclasts. Indeed,
CD38 was lost during in vitro osteoclastogenesis. Consistently, we found that
Daratumumab reacted with CD38 expressed on monocytes and its binding inhibited in
vitro osteoclastogenesis and bone resorption activity from bone marrow total
mononuclear cells of MM patients, targeting early osteoclast progenitors. The
inhibitory effect was not observed from purified CD14(+) cells, suggesting an
indirect inhibitory effect of Daratumumab. Interestingly, all-trans retinoic acid
treatment increased the inhibitory effect of Daratumumab on osteoclast formation.
These observations provide a rationale for the use of an anti-CD38 antibody-based
approach as treatment for multiple myeloma-induced osteoclastogenesis.