Aim: Waldenström macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by overproduction of monoclonal IgM. To date, there are no therapies that provide a cure for WM patients, and therefore, it is important to explore new therapies. Little is known about the efficiency of epigenetic targeting in WM. Materials & methods: WM cells were treated with BET inhibitors (JQ1 and I-BET-762) and venetoclax, panobinostat or ibrutinib. Results: BET inhibition reduces growth of WM cells, with little effect on survival. This finding was enhanced by combination therapy, with panobinostat (LBH589) showing the highest synergy. Conclusion: Our studies identify BET inhibitors as effective therapy for WM, and these inhibitors can be enhanced in combination with BCL2 or histone deacetylase inhibition.
Aim: Waldenström macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by overproduction of monoclonal IgM. To date, there are no therapies that provide a cure for WM patients, and therefore, it is important to explore new therapies. Little is known about the efficiency of epigenetic targeting in WM. Materials & methods: WM cells were treated with BET inhibitors (JQ1 and I-BET-762) and venetoclax, panobinostat or ibrutinib. Results: BET inhibition reduces growth of WM cells, with little effect on survival. This finding was enhanced by combination therapy, with panobinostat (LBH589) showing the highest synergy. Conclusion: Our studies identify BET inhibitors as effective therapy for WM, and these inhibitors can be enhanced in combination with BCL2 or histone deacetylase inhibition.
Entities:
Keywords:
BET inhibitors; Waldenström macroglobulinemia; epigenetics; panobinostat; venetoclax
Authors: Alexandre Puissant; Stacey M Frumm; Gabriela Alexe; Christopher F Bassil; Jun Qi; Yvan H Chanthery; Erin A Nekritz; Rhamy Zeid; William Clay Gustafson; Patricia Greninger; Matthew J Garnett; Ultan McDermott; Cyril H Benes; Andrew L Kung; William A Weiss; James E Bradner; Kimberly Stegmaier Journal: Cancer Discov Date: 2013-02-21 Impact factor: 39.397
Authors: Steven P Treon; Christina K Tripsas; Kirsten Meid; Diane Warren; Gaurav Varma; Rebecca Green; Kimon V Argyropoulos; Guang Yang; Yang Cao; Lian Xu; Christopher J Patterson; Scott Rodig; James L Zehnder; Jon C Aster; Nancy Lee Harris; Sandra Kanan; Irene Ghobrial; Jorge J Castillo; Jacob P Laubach; Zachary R Hunter; Zeena Salman; Jianling Li; Mei Cheng; Fong Clow; Thorsten Graef; M Lia Palomba; Ranjana H Advani Journal: N Engl J Med Date: 2015-04-09 Impact factor: 91.245
Authors: C Escot; C Theillet; R Lidereau; F Spyratos; M H Champeme; J Gest; R Callahan Journal: Proc Natl Acad Sci U S A Date: 1986-07 Impact factor: 11.205
Authors: Lian Xu; Zachary R Hunter; Guang Yang; Yangsheng Zhou; Yang Cao; Xia Liu; Enrica Morra; Alessandra Trojani; Antonino Greco; Luca Arcaini; Marzia Varettoni; Maria Varettoni; Jennifer R Brown; Yu-Tzu Tai; Kenneth C Anderson; Nikhil C Munshi; Christopher J Patterson; Robert J Manning; Christina K Tripsas; Neal I Lindeman; Steven P Treon Journal: Blood Date: 2013-01-15 Impact factor: 22.113
Authors: Michael L Wang; Simon Rule; Peter Martin; Andre Goy; Rebecca Auer; Brad S Kahl; Wojciech Jurczak; Ranjana H Advani; Jorge E Romaguera; Michael E Williams; Jacqueline C Barrientos; Ewa Chmielowska; John Radford; Stephan Stilgenbauer; Martin Dreyling; Wieslaw Wiktor Jedrzejczak; Peter Johnson; Stephen E Spurgeon; Lei Li; Liang Zhang; Kate Newberry; Zhishuo Ou; Nancy Cheng; Bingliang Fang; Jesse McGreivy; Fong Clow; Joseph J Buggy; Betty Y Chang; Darrin M Beaupre; Lori A Kunkel; Kristie A Blum Journal: N Engl J Med Date: 2013-06-19 Impact factor: 91.245
Authors: Daniela Drandi; Philippe Decruyenaere; Martina Ferrante; Fritz Offner; Jo Vandesompele; Simone Ferrero Journal: Diagnostics (Basel) Date: 2022-04-12
Authors: Stephan J Matissek; Mona Karbalivand; Weiguo Han; Ava Boutilier; Estefania Yzar-Garcia; Laura L Kehoe; Devin Storm Gardner; Adam Hage; Krista Fleck; Vicki Jeffers; Ricardo Rajsbaum; Sherine F Elsawa Journal: Oncotarget Date: 2022-08-03