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@article{1404545,
author = {Plešingerová, Hana and Janovská, Pavlína and Mishra, Ashish Kumar and Smyčková, Lucie and Poppová, Lucie and Libra, A. and Plevová, Karla and Ovesná, Petra and Radová, Lenka and Doubek, Michael and Pavlová, Šárka and Pospíšilová, Šárka and Bryja, Vítězslav},
article_number = {2},
doi = {http://dx.doi.org/10.3324/haematol.2017.178699},
keywords = {CHIMERIC ANTIGEN RECEPTOR; B-CELLS; MUTATIONAL STATUS; T-CELLS; GENE; CLL; PATHWAY; DIFFERENTIATION; PATHOGENESIS; CHEMOTAXIS},
language = {eng},
issn = {0390-6078},
journal = {Haematologica/the hematology journal},
title = {Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia},
url = {http://dx.doi.org/10.3324/haematol.2017.178699},
volume = {103},
year = {2018}
}
TY - JOUR
ID - 1404545
AU - Plešingerová, Hana - Janovská, Pavlína - Mishra, Ashish Kumar - Smyčková, Lucie - Poppová, Lucie - Libra, A. - Plevová, Karla - Ovesná, Petra - Radová, Lenka - Doubek, Michael - Pavlová, Šárka - Pospíšilová, Šárka - Bryja, Vítězslav
PY - 2018
TI - Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia
JF - Haematologica/the hematology journal
VL - 103
IS - 2
SP - 313-324
EP - 313-324
PB - Fondazione Ferrata Storti
SN - 03906078
KW - CHIMERIC ANTIGEN RECEPTOR
KW - B-CELLS
KW - MUTATIONAL STATUS
KW - T-CELLS
KW - GENE
KW - CLL
KW - PATHWAY
KW - DIFFERENTIATION
KW - PATHOGENESIS
KW - CHEMOTAXIS
UR - http://dx.doi.org/10.3324/haematol.2017.178699
N2 - Chronic lymphocytic leukemia is a disease with up-regulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low. Importantly, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 have an unfavorable disease course with short overall survival and time to second treatment. COBLL1 serves as an independent molecular marker for overall survival in chronic lymphocytic leukemia patients with unmutated IGHV. In addition, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 show impaired motility and chemotaxis towards CCL19 and CXCL12 as well as enhanced B-cell receptor signaling pathway activation demonstrated by increased PLC gamma 2 and SYK phosphorylation after IgM stimulation. COBLL1 expression also changes during B-cell maturation in non-malignant secondary lymphoid tissue with a higher expression in germinal center B cells than naive and memory B cells. Our data thus suggest COBLL1 involvement not only in chronic lymphocytic leukemia but also in B-cell development. In summary, we show that expression of COBLL1, encoding novel ROR1-binding partner, defines chronic lymphocytic leukemia sub-groups with a distinct response to microenvironmental stimuli, and independently predicts survival of chronic lymphocytic leukemia with unmutated IGHV.
ER -
PLEŠINGEROVÁ, Hana, Pavlína JANOVSKÁ, Ashish Kumar MISHRA, Lucie SMYČKOVÁ, Lucie POPPOVÁ, A. LIBRA, Karla PLEVOVÁ, Petra OVESNÁ, Lenka RADOVÁ, Michael DOUBEK, Šárka PAVLOVÁ, Šárka POSPÍŠILOVÁ and Vítězslav BRYJA. Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia (Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia.). \textit{Haematologica/the hematology journal}. Fondazione Ferrata Storti, 2018, vol.~103, No~2, p.~313-324. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2017.178699.
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