BACKGROUND: Signaling through the B-cell receptor appears to be a major contributor to the pathogenesis of chronic lymphocytic leukemia. Toll-like receptors bridge the innate and adaptive immune responses by acting as co-stimulatory signals for B cells. The available data on the expression of Toll-like receptors in chronic lymphocytic leukemia are limited and derive from small series of patients. DESIGN AND METHODS: We profiled the expression of genes associated with Toll-like receptor signaling pathways in 192 cases of chronic lymphocytic leukemia and explored potential associations with molecular features of the clonotypic B-cell receptors. RESULTS: Chronic lymphocytic leukemia cells express all Toll-like receptors expressed by normal activated B cells, with high expression of TLR7 and CD180, intermediate expression of TLR1, TLR6, TLR10 and low expression of TLR2 and TLR9. The vast majority of adaptors, effectors and members of the NFKB, JNK/p38, NF/IL6 and IRF pathways are intermediately-to-highly expressed, while inhibitors of Toll-like receptor activity are generally low-to-undetectable, indicating that the Toll-like receptor-signaling framework is competent in chronic lymphocytic leukemia. Significant differences were identified for selected genes between cases carrying mutated or unmutated IGHV genes or assigned to different subsets with stereotyped B-cell receptors. The differentially expressed molecules include receptors, NFκB/MAPK signaling molecules and final targets of the cascade. CONCLUSIONS: The observed variations are suggestive of distinctive activation patterns of the Toll-like receptor signaling pathway in subgroups of cases of chronic lymphocytic leukemia defined by the molecular features of B-cell receptors. Additionally, they indicate that different or concomitant signals acting through receptors other than the B-cell receptor can affect the behavior of the malignant clone.
BACKGROUND: Signaling through the B-cell receptor appears to be a major contributor to the pathogenesis of chronic lymphocytic leukemia. Toll-like receptors bridge the innate and adaptive immune responses by acting as co-stimulatory signals for B cells. The available data on the expression of Toll-like receptors in chronic lymphocytic leukemia are limited and derive from small series of patients. DESIGN AND METHODS: We profiled the expression of genes associated with Toll-like receptor signaling pathways in 192 cases of chronic lymphocytic leukemia and explored potential associations with molecular features of the clonotypic B-cell receptors. RESULTS:Chronic lymphocytic leukemia cells express all Toll-like receptors expressed by normal activated B cells, with high expression of TLR7 and CD180, intermediate expression of TLR1, TLR6, TLR10 and low expression of TLR2 and TLR9. The vast majority of adaptors, effectors and members of the NFKB, JNK/p38, NF/IL6 and IRF pathways are intermediately-to-highly expressed, while inhibitors of Toll-like receptor activity are generally low-to-undetectable, indicating that the Toll-like receptor-signaling framework is competent in chronic lymphocytic leukemia. Significant differences were identified for selected genes between cases carrying mutated or unmutated IGHV genes or assigned to different subsets with stereotyped B-cell receptors. The differentially expressed molecules include receptors, NFκB/MAPK signaling molecules and final targets of the cascade. CONCLUSIONS: The observed variations are suggestive of distinctive activation patterns of the Toll-like receptor signaling pathway in subgroups of cases of chronic lymphocytic leukemia defined by the molecular features of B-cell receptors. Additionally, they indicate that different or concomitant signals acting through receptors other than the B-cell receptor can affect the behavior of the malignant clone.
Authors: Anna Lanemo Myhrinder; Eva Hellqvist; Ekaterina Sidorova; Anita Söderberg; Helen Baxendale; Charlotte Dahle; Kerstin Willander; Gerard Tobin; Eva Bäckman; Ola Söderberg; Richard Rosenquist; Sohvi Hörkkö; Anders Rosén Journal: Blood Date: 2008-01-25 Impact factor: 22.113
Authors: P G Longo; L Laurenti; S Gobessi; A Petlickovski; M Pelosi; P Chiusolo; S Sica; G Leone; D G Efremov Journal: Leukemia Date: 2006-10-05 Impact factor: 11.528
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Authors: Kwan-Ki Hwang; Xi Chen; Daniel M Kozink; Marietta Gustilo; Dawn J Marshall; John F Whitesides; Hua-Xin Liao; Rosa Catera; Charles C Chu; Xiao-Jie Yan; Micah A Luftig; Barton F Haynes; Nicholas Chiorazzi Journal: Blood Date: 2011-12-12 Impact factor: 22.113
Authors: J Claire Godbersen; Leigh Ann Humphries; Olga V Danilova; Peter E Kebbekus; Jennifer R Brown; Alan Eastman; Alexey V Danilov Journal: Clin Cancer Res Date: 2014-03-15 Impact factor: 12.531
Authors: Lesley-Ann Sutton; Emma Young; Panagiotis Baliakas; Anastasia Hadzidimitriou; Theodoros Moysiadis; Karla Plevova; Davide Rossi; Jana Kminkova; Evangelia Stalika; Lone Bredo Pedersen; Jitka Malcikova; Andreas Agathangelidis; Zadie Davis; Larry Mansouri; Lydia Scarfò; Myriam Boudjoghra; Alba Navarro; Alice F Muggen; Xiao-Jie Yan; Florence Nguyen-Khac; Marta Larrayoz; Panagiotis Panagiotidis; Nicholas Chiorazzi; Carsten Utoft Niemann; Chrysoula Belessi; Elias Campo; Jonathan C Strefford; Anton W Langerak; David Oscier; Gianluca Gaidano; Sarka Pospisilova; Frederic Davi; Paolo Ghia; Kostas Stamatopoulos; Richard Rosenquist Journal: Haematologica Date: 2016-05-19 Impact factor: 9.941
Authors: Meena Kanduri; Millaray Marincevic; Anna M Halldórsdóttir; Larry Mansouri; Katarina Junevik; Stavroula Ntoufa; Hanna Göransson Kultima; Anders Isaksson; Gunnar Juliusson; Per-Ola Andersson; Hans Ehrencrona; Kostas Stamatopoulos; Richard Rosenquist Journal: Epigenetics Date: 2012-11-15 Impact factor: 4.528