PMID- 27411688
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20181202
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 104
IP  - 3
DP  - 2016 Sep
TI  - Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple 
      myeloma.
PG  - 281-92
LID - 10.1007/s12185-016-2048-5 [doi]
AB  - Multiple myeloma cells acquire the resistance to anti-cancer drugs through 
      physical and functional interactions with the bone marrow microenvironment via 
      two overlapping mechanisms. First, bone marrow stromal cells (BMSCs) produce 
      soluble factors, such as interleukin-6 and insulin-like growth factor-1, to 
      activate signal transduction pathways leading to drug resistance (soluble 
      factor-mediated drug resistance). Second, BMSCs up-regulate the expression of 
      cell cycle inhibitors, anti-apoptotic members of the Bcl-2 family and ABC drug 
      transporters in myeloma cells upon direct adhesion [cell adhesion-mediated drug 
      resistance (CAM-DR)]. Elucidation of the mechanisms underlying drug resistance 
      may greatly contribute to the advancement of cancer therapies. Recent 
      investigations, including ours, have revealed the involvement of epigenetic 
      alterations in drug resistance especially CAM-DR. For example, we found that 
      class I histone deacetylases (HDACs) determine the sensitivity of proteasome 
      inhibitors and the histone methyltransferase EZH2 regulates the transcription of 
      anti-apoptotic genes during the acquisition of CAM-DR by myeloma cells. In 
      addition, another histone methyltransferase MMSET was shown to confer drug 
      resistance to myeloma cells by facilitating DNA repair. These findings provide a 
      rationale for the inclusion of epigenetic drugs, such as HDAC inhibitors and 
      histone methylation modifiers, in combination chemotherapy for MM patients to 
      increase the therapeutic index.
FAU - Furukawa, Yusuke
AU  - Furukawa Y
AD  - Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical 
      University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. 
      furuyu@jichi.ac.jp.
FAU - Kikuchi, Jiro
AU  - Kikuchi J
AD  - Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical 
      University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160713
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Bone Marrow Cells/cytology/physiology
MH  - Cell Adhesion/*physiology
MH  - Drug Resistance, Neoplasm/*genetics
MH  - *Epigenesis, Genetic
MH  - Histone Deacetylases/metabolism
MH  - Histone Methyltransferases
MH  - Histone-Lysine N-Methyltransferase/metabolism
MH  - Humans
MH  - Multiple Myeloma/*drug therapy/pathology
MH  - Stromal Cells/cytology/metabolism/physiology
OTO - NOTNLM
OT  - Bone marrow microenvironment
OT  - Epigenetics
OT  - Histone deacetylase
OT  - Histone methyltransferase
EDAT- 2016/07/15 06:00
MHDA- 2017/03/17 06:00
CRDT- 2016/07/15 06:00
PHST- 2016/06/16 00:00 [received]
PHST- 2016/06/17 00:00 [accepted]
PHST- 2016/07/15 06:00 [entrez]
PHST- 2016/07/15 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
AID - 10.1007/s12185-016-2048-5 [pii]
AID - 10.1007/s12185-016-2048-5 [doi]
PST - ppublish
SO  - Int J Hematol. 2016 Sep;104(3):281-92. doi: 10.1007/s12185-016-2048-5. Epub 2016 
      Jul 13.