Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.

Blood
Nakhle S SabaAdrian Wiestner

Abstract

To interrogate signaling pathways activated in mantle cell lymphoma (MCL) in vivo, we contrasted gene expression profiles of 55 tumor samples isolated from blood and lymph nodes from 43 previously untreated patients with active disease. In addition to lymph nodes, MCL often involves blood, bone marrow, and spleen and is incurable for most patients. Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL. However, the role of specific signaling pathways in the lymphomagenesis of MCL and the biologic basis for ibrutinib sensitivity of these tumors are unknown. Here, we demonstrate activation of B-cell receptor (BCR) and canonical NF-κB signaling specifically in MCL cells in the lymph node. Quantification of BCR signaling strength, reflected in the expression of BCR regulated genes, identified a subset of patients with inferior survival after cytotoxic therapy. Tumor proliferation was highest in the lymph node and correlated with the degree of BCR activation. A subset of leukemic tumors showed active BCR and NF-κB signaling apparently independent of microenvironmental support. In one of these samples, we identified a novel somatic mutation in RELA (E39Q). This sample was resis...Continue Reading

References

Jul 12, 2002·The New England Journal of Medicine·Olivier HermineXavier Troussard
Feb 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter MartinJohn P Leonard
Aug 31, 2010·Nucleic Acids Research·Kai WangJinze Liu
Jun 30, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marc A WenigerAdrian Wiestner
Aug 31, 2012·The New England Journal of Medicine·Steven P TreonZachary R Hunter
Oct 2, 2012·The Journal of Clinical Investigation·Pedro JaresElias Campo
Oct 10, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ranjana AdvaniNathan Fowler
Oct 10, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adrian Wiestner
Feb 15, 2013·Blood·Barbara MeissnerRandy D Gascoyne
Apr 9, 2013·Hematology/oncology Clinics of North America·Yair HerishanuAdrian Wiestner
Jun 21, 2013·The New England Journal of Medicine·Michael WangKristie A Blum
Jun 21, 2013·The New England Journal of Medicine·John C ByrdSusan O'Brien
Oct 19, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·V Camara-ClayetteVincent Ribrag
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Silvia BeaElias Campo
Apr 2, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eva HosterMichael Unterhalt
May 27, 2014·Current Opinion in Hematology·Nakhle S Saba, Adrian Wiestner
Dec 17, 2014·Blood·Elias Campo, Martin Dreyling
Feb 26, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Thomas E WitzigM S Czuczman
Apr 9, 2015·The New England Journal of Medicine·Steven P TreonRanjana Advani
Jul 21, 2015·Nature Medicine·Wyndham H WilsonLouis M Staudt
Jul 22, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John G GribbenFranck Morschhauser

Citations

Nov 30, 2016·Leukemia & Lymphoma·Niklas VogtGeorg Lenz
Apr 11, 2017·Journal of Internal Medicine·P GhiaF K Stevenson
May 18, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas E Witzig
Feb 15, 2018·Targeted Oncology·Valentina RestelliLaura Carrassa
Jan 24, 2018·British Journal of Haematology·Oshrat Hershkovitz-RokahOfer Shpilberg
Oct 19, 2017·Journal of Hematology & Oncology·Michael FichtnerMartin Trepel
May 9, 2018·Expert Review of Hematology·Farrukh T Awan, Wojciech Jurczak
Aug 3, 2019·Expert Opinion on Pharmacotherapy·Piotr SmolewskiTadeusz Robak
Jan 20, 2018·Nature Reviews. Cancer·Jan A Burger, Adrian Wiestner
Feb 28, 2020·Cells·Oriol de BarriosMaribel Parra
Apr 24, 2020·Expert Opinion on Investigational Drugs·Clémentine Sarkozy, Vincent Ribrag
Jun 18, 2020·Cancers·Gaël Roué, Brigitte Sola
Jun 24, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah C PyfromJacqueline E Payton
Aug 16, 2018·F1000Research·Michael SchieberReem Karmali
Mar 16, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David W ScottLymphoma/Leukemia Molecular Profiling Project
Apr 10, 2019·American Journal of Hematology·Preetesh Jain, Michael Wang
Jun 17, 2018·Journal of Hematology & Oncology·Swathi BalajiMichael Wang
Mar 22, 2020·International Journal of Molecular Sciences·Pavel Klener, Magdalena Klanova
Jul 21, 2020·Clinical & Translational Immunology·Ziduo LiGeorgina J Clark
Jun 8, 2019·Histopathology·Georgios PetrakisElias Campo
Feb 28, 2018·Molecular Cancer Therapeutics·Jiyu GuanSam Okret
Oct 14, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Santiago DemajoPedro Jares
Dec 29, 2020·Frontiers in Oncology·Lorenz ThurnerMoritz Bewarder
Mar 8, 2021·Journal of Hematology & Oncology·Danling GuYi Miao
Mar 14, 2021·American Journal of Clinical Pathology·Audrey N JajoskyHoward J Meyerson
May 1, 2021·Nature Cancer·Christine S MoonAdolfo A Ferrando

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