| MRÁZ, Marek, Clive ZENT, Amy CHURCH, Diane JELINEK, Xiaosheng WU, Šárka POSPÍŠILOVÁ, Stephen ANSELL, Anne NOVAK, Neil KAY, Thomas WITZIG a Grzegorz NOWAKOWSKI. Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alfa-4-beta-1 (VLA4) with natalizumab can overcome this resistance. British Journal of Haematology. Wiley-Blackwell, 2011, roč. 155, č. 1, s. 53-64. ISSN 0007-1048. Dostupné z: https://dx.doi.org/10.1111/j.1365-2141.2011.08794.x. |
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@article{965639,
author = {Mráz, Marek and Zent, Clive and Church, Amy and Jelinek, Diane and Wu, Xiaosheng and Pospíšilová, Šárka and Ansell, Stephen and Novak, Anne and Kay, Neil and Witzig, Thomas and Nowakowski, Grzegorz},
article_number = {1},
doi = {http://dx.doi.org/10.1111/j.1365-2141.2011.08794.x},
keywords = {lymphoma; stromal cells; cell adhesion-mediated drug resistance; rituximab; natalizumab},
language = {eng},
issn = {0007-1048},
journal = {British Journal of Haematology},
title = {Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alfa-4-beta-1 (VLA4) with natalizumab can overcome this resistance},
url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08794.x/abstract},
volume = {155},
year = {2011}
}
TY - JOUR
ID - 965639
AU - Mráz, Marek - Zent, Clive - Church, Amy - Jelinek, Diane - Wu, Xiaosheng - Pospíšilová, Šárka - Ansell, Stephen - Novak, Anne - Kay, Neil - Witzig, Thomas - Nowakowski, Grzegorz
PY - 2011
TI - Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alfa-4-beta-1 (VLA4) with natalizumab can overcome this resistance
JF - British Journal of Haematology
VL - 155
IS - 1
SP - 53-64
EP - 53-64
PB - Wiley-Blackwell
SN - 00071048
KW - lymphoma
KW - stromal cells
KW - cell adhesion-mediated drug resistance
KW - rituximab
KW - natalizumab
UR - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08794.x/abstract
L2 - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08794.x/abstract
N2 - 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.
ER -
MRÁZ, Marek, Clive ZENT, Amy CHURCH, Diane JELINEK, Xiaosheng WU, Šárka POSPÍŠILOVÁ, Stephen ANSELL, Anne NOVAK, Neil KAY, Thomas WITZIG a Grzegorz NOWAKOWSKI. Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alfa-4-beta-1 (VLA4) with natalizumab can overcome this resistance. \textit{British Journal of Haematology}. Wiley-Blackwell, 2011, roč.~155, č.~1, s.~53-64. ISSN~0007-1048. Dostupné z: https://dx.doi.org/10.1111/j.1365-2141.2011.08794.x.
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