PMID- 32759572
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20200924
IS  - 0485-1439 (Print)
IS  - 0485-1439 (Linking)
VI  - 61
IP  - 7
DP  - 2020
TI  - [Toll-like receptor CD180 and the bone marrow microenvironment as therapeutic 
      targets in multiple myeloma].
PG  - 832-841
LID - 10.11406/rinketsu.61.832 [doi]
AB  - Multiple myeloma (MM) is among the most intractable of malignancies and is 
      characterized by uncontrolled growth of malignant plasma cells in the bone marrow 
      (BM). Elucidation of the mechanisms underlying cell adhesion-mediated drug 
      resistance (CAM-DR) may prolong remission and ultimately improve the survival of 
      MM patients. Toward this goal, we identified trimethylation of histone H3 at 
      lysine-27 (H3K27me3) as a critical histone modification associated with CAM-DR. 
      Cell adhesion counteracted drug-induced hypermethylation of H3K27 via inhibiting 
      phosphorylation of enhancer of zeste homolog 2 (EZH2), and promoted sustained 
      expression of anti-apoptotic genes. In addition, we found that CD180, a 
      non-canonical lipopolysaccharide (LPS) receptor, was markedly up-regulated in 
      response to adherence and/or hypoxic conditions. Bacterial LPS enhanced the 
      growth of MM cells both in vitro and in vivo, correlating with expression of 
      CD180. Promoter analyses identified Ikaros (IKZF1) as a pivotal transcriptional 
      activator of the CD180 gene; expression of CD180 was activated via cell adhesion- 
      and/or hypoxia-mediated increases in IKZF1 expression. Administration of 
      lenalidomide prevented the LPS-triggered activation of MM cells by targeting 
      CD180. Taken together, our results suggest that lenalidomide-mediated prevention 
      of LPS-triggered disease progression may be an effective means for prolonging 
      survival in patients with MM.
FAU - Kikuchi, Jiro
AU  - Kikuchi J
AD  - Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical 
      University.
FAU - Furukawa, Yusuke
AU  - Furukawa Y
AD  - Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical 
      University.
LA  - jpn
PT  - Journal Article
PL  - Japan
TA  - Rinsho Ketsueki
JT  - [Rinsho ketsueki] The Japanese journal of clinical hematology
JID - 2984782R
RN  - 0 (Antigens, CD)
RN  - 0 (CD180 protein, human)
RN  - 0 (Histones)
RN  - 0 (Toll-Like Receptors)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Antigens, CD
MH  - Bone Marrow
MH  - Histones
MH  - Humans
MH  - Lenalidomide
MH  - *Multiple Myeloma
MH  - Toll-Like Receptors
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - Bone marrow microenvironment
OT  - CD180
OT  - Drug resistance
OT  - Epigenetics
EDAT- 2020/08/08 06:00
MHDA- 2020/09/25 06:00
CRDT- 2020/08/08 06:00
PHST- 2020/08/08 06:00 [entrez]
PHST- 2020/08/08 06:00 [pubmed]
PHST- 2020/09/25 06:00 [medline]
AID - 10.11406/rinketsu.61.832 [doi]
PST - ppublish
SO  - Rinsho Ketsueki. 2020;61(7):832-841. doi: 10.11406/rinketsu.61.832.