PMID- 21749361
OWN - NLM
STAT- MEDLINE
DCOM- 20140509
LR  - 20211020
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 155
IP  - 1
DP  - 2011 Oct
TI  - Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced 
      apoptosis and targeting integrin alpha-4-beta-1 (VLA-4) with natalizumab can overcome 
      this resistance.
PG  - 53-64
LID - 10.1111/j.1365-2141.2011.08794.x [doi]
AB  - Rituximab improves the outcome of patients with non-Hodgkin lymphoma, but does 
      not completely eradicate residual B-cell populations in the microenvironment of 
      the bone marrow and lymph nodes. Adhesion to stromal cells can protect B-cells 
      from apoptosis induced by chemotherapy drugs [(cell adhesion-mediated drug 
      resistance (CAM-DR)]. A similar mechanism of resistance to rituximab has not, to 
      our knowledge, been described. We tested the hypothesis that the microenvironment 
      protects malignant B-cells from rituximab-induced apoptosis, and that blocking 
      these interactions with natalizumab, an antibody targeting VLA-4 (integrin 
      alfa-4-beta-1/CD49d), can overcome this protection. VLA-4 is an adhesion molecule 
      constitutively expressed on malignant B-cells and is important for pro-survival 
      signalling in the bone marrow and lymph node microenvironment. The human bone 
      marrow stromal cell line HS-5 was shown to strongly protect B-cell lymphoma cells 
      from rituximab cytotoxicity, suggesting the existence of a stromal cell 
      adhesion-mediated antibody resistance (CAM-AR) mechanism analogous to CAM-DR. 
      Natalizumab decreased B-lymphocyte adherence to fibronectin by 75-95% and 
      partially overcame stromal protection against rituximab and cytotoxic drugs. 
      These pre-clinical findings suggest that the addition of stromal 
      adhesion-disruptive drugs to rituximab-containing therapy could improve treatment 
      efficacy.
CI  - (c) 2011 Blackwell Publishing Ltd.
FAU - Mraz, Marek
AU  - Mraz M
AD  - Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, 
      USA.
FAU - Zent, Clive S
AU  - Zent CS
FAU - Church, Amy K
AU  - Church AK
FAU - Jelinek, Diane F
AU  - Jelinek DF
FAU - Wu, Xiaosheng
AU  - Wu X
FAU - Pospisilova, Sarka
AU  - Pospisilova S
FAU - Ansell, Stephen M
AU  - Ansell SM
FAU - Novak, Anne J
AU  - Novak AJ
FAU - Kay, Neil E
AU  - Kay NE
FAU - Witzig, Thomas E
AU  - Witzig TE
FAU - Nowakowski, Grzegorz S
AU  - Nowakowski GS
LA  - eng
GR  - P50 CA097274/CA/NCI NIH HHS/United States
GR  - P50 CA097274-09/CA/NCI NIH HHS/United States
GR  - CA097274/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110712
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Integrin alpha4beta1)
RN  - 0 (Natalizumab)
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/pharmacology
MH  - Antibodies, Monoclonal, Murine-Derived/*pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects/physiology
MH  - B-Lymphocytes/drug effects/physiology
MH  - Bone Marrow Cells/physiology
MH  - Cell Adhesion/drug effects
MH  - Coculture Techniques
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Humans
MH  - Integrin alpha4beta1/antagonists & inhibitors/physiology
MH  - Lymphoma, B-Cell/drug therapy/*pathology
MH  - Natalizumab
MH  - Rituximab
MH  - Stromal Cells/*physiology
MH  - Tumor Cells, Cultured
MH  - Tumor Microenvironment/drug effects
PMC - PMC4405035
MID - NIHMS301497
EDAT- 2011/07/14 06:00
MHDA- 2014/05/10 06:00
PMCR- 2015/04/21
CRDT- 2011/07/14 06:00
PHST- 2011/07/14 06:00 [entrez]
PHST- 2011/07/14 06:00 [pubmed]
PHST- 2014/05/10 06:00 [medline]
PHST- 2015/04/21 00:00 [pmc-release]
AID - 10.1111/j.1365-2141.2011.08794.x [doi]
PST - ppublish
SO  - Br J Haematol. 2011 Oct;155(1):53-64. doi: 10.1111/j.1365-2141.2011.08794.x. Epub 
      2011 Jul 12.