POTENTIAL THERAPEUTIC ADVANTAGE FOR DUVELISIB IN MANTLE CELL LYMPHOMA: PI3Kδ AND OVEREXPRESSED PI3Kγ IN LYMPHOMA CELLS HAVE SPECIALIZED FUNCTIONAL ROLES

2019 ◽  
Vol 37 ◽  
pp. 511-512
Author(s):  
K.J. Till ◽  
J. Gallardo Zapata ◽  
T. Marks ◽  
D.T. Weaver ◽  
J.A. Pachter ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphoma Cells ◽  
Functional Roles ◽  
Therapeutic Advantage ◽  
Mantle Cell

scholarly journals The G protein-coupled estrogen receptor 1 (GPER-1) contributes to the proliferation and survival of mantle cell lymphoma cells

Haematologica ◽  
2015 ◽  
Vol 100 (11) ◽  
pp. e458-e461 ◽  
Author(s):  
M. Rudelius ◽  
H. Rauert-Wunderlich ◽  
E. Hartmann ◽  
E. Hoster ◽  
M. Dreyling ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mantle Cell Lymphoma ◽  
G Protein ◽  
Cell Lymphoma ◽  
Lymphoma Cells ◽  
Mantle Cell ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals Ibrutinib-Induced Egression of Large/Blastoid Mantle Cell Lymphoma Cells Into Peripheral Circulation

2014 ◽  
Vol 142 (suppl_1) ◽  
pp. A099-A099
Author(s):  
Jindong Wang ◽  
Viren Patel ◽  
Siddharth Bhattacharyya ◽  
Ashish Bains
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Peripheral Circulation ◽  
Lymphoma Cells ◽  
Mantle Cell

scholarly journals Functional cooperativity of p97 and histone deacetylase 6 in mediating DNA repair in mantle cell lymphoma cells

Leukemia ◽  
2019 ◽  
Vol 33 (7) ◽  
pp. 1675-1686 ◽  
Author(s):  
Pratikkumar H. Vekaria ◽  
Amar Kumar ◽  
Dharmalingam Subramaniam ◽  
Neil Dunavin ◽  
Anusha Vallurupalli ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mantle Cell Lymphoma ◽  
Histone Deacetylase ◽  
Cell Lymphoma ◽  
Histone Deacetylase 6 ◽  
Lymphoma Cells ◽  
Mantle Cell

scholarly journals Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib

Blood ◽  
2015 ◽  
Vol 126 (13) ◽  
pp. 1565-1574 ◽  
Author(s):  
Baohua Sun ◽  
Bhavin Shah ◽  
Warren Fiskus ◽  
Jun Qi ◽  
Kimal Rajapakshe ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Histone Deacetylases ◽  
Cell Lymphoma ◽  
Synergistic Activity ◽  
Lymphoma Cells ◽  
Key Points ◽  
Mantle Cell ◽  
Bet Protein

Key Points BA reduces MYC, CDK4/6, nuclear RelA, and BTK expression and is synergistically lethal with ibrutinib in MCL cells. Cotreatment with BA and inhibitor of BCL2, CDK4/6, or histone deacetylases is synergistically lethal against ibrutinib-resistant MCL cells.

The Tak-1 Inhibitor AZ-Tak1 Inhibits XIAP, Activates Caspase-9, and Induces Apoptosis in Mantle Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1692-1692 ◽  
Author(s):  
Daniela Buglio ◽  
Sangeetha Palakurthi ◽  
Katharine F. Byth ◽  
Anas Younes
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Small Molecule ◽  
Cell Lymphoma ◽  
Small Molecule Inhibitor ◽  
Caspase 9 ◽  
Lymphoma Cells ◽  
Molecule Inhibitor ◽  
Mantle Cell ◽  
Induced Apoptosis

Abstract Abstract 1692 Poster Board I-718 Transforming growth factor-b-activated kinase 1 (TAK1) is a key regulator of NF-kB activation. TAK1 can be activated by a variety of pro-inflammatory cytokines and T and B cell receptors. Recent experiments demonstrated that deletion of TAK1 results in inactivation of both JNK and NF-kB signaling resulting in massive apoptotic death of hematopoietic cells in mice. In this study, we examined the expression pattern of TAK1 and its role as a potential therapeutic target for lymphoma. First, we examined TAK1 expression in a panel of lymphoid cell lines by western blot, and found it to be highly expressed in mantle cell lymphoma cell lines (Mino, SP53, and Jeko-1). These lines expressed relatively low levels of the tumor suppressor protein A20. Mino and SP53 expressed high level of p-p38. Subsequently, we investigated the in vitro activity of the novel TAK1 small molecule inhibitor AZ-Tak1 in these cell lines. AZ-Tak1 is a potent and a relatively selective inhibitor of TAK1 kinase activity, with an IC50 of 0.009 mM. It also inhibits Jak2 but at a much higher concentration (IC50=0.18 mM). AZ-Tak1 treatment decreased the level of p38 and ERK in mantle cell lymphoma cells, and induced apoptosis in a dose and time dependent manner, with an IC50 of 0.1-0.5 mM. Using the annexin-V and PI staining and FACS analysis, After 48 hours of incubation, AZ-Tak1 (0.1 mM) induced apoptosis in 28%, 34% and 86% of Mino, SP53, and Jeko cells, respectively, which was increased to 32%, 42%, and 86% when 0.5 mM concentration was used. Similar activity was also observed when primary mantle cell lymphoma cells were examined. Using pathway-specific protein arrays focusing on apoptosis, kinases, and transcription factors, AZ-Tak1 (0.5 mM) altered the level of several proteins that regulate cell growth and survival, especially members of the inhibitors of apoptosis (IAP) family. Specifically, AZ-Tak1 decreased the level of SMAC/DIABOLO and cytochrome –C in the mitochondria, which was associated with a decrease in the level of the anti-apoptotic protein X-linked IAP (XIAP) and activation of the intrinsic apoptotic pathway as evident by activation of caspase 9, cleavage of caspase 3, and induction of apoptosis. Furthermore, and consistant with its ability to inhibit Jak2 activity, AZ-Tak1 reduced STAT2 and STAT6 levels. AZ-Tak1 demonstrated no significant effect on bcl-2 family members. Finally, co-treatment with HDAC inhibitors demonstrated synergistic effect with low concentrations of AZ-Tak1. Collectively, our data demonstrate that targeting TAK1 by the small molecule inhibitor AZ-Tak1 induces cell death in mantle cell lymphoma by activating the intrinsic apoptosis pathway, suggesting that targeting TAK1 may have a therapeutic value for the treatment of mantle cell lymphoma. Disclosures Palakurthi: Astra Zeneca: Employment. Byth:Astra Zeneca : Employment.

Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo

2011 ◽  
Vol 35 (3) ◽  
pp. 380-386 ◽  
Author(s):  
Zhengzi Qian ◽  
Liang Zhang ◽  
Zhen Cai ◽  
Luhong Sun ◽  
Huaqing Wang ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Growth Arrest ◽  
Lymphoma Cells ◽  
Mantle Cell ◽  
Induce Growth Arrest

850 Autophagy Inhibition Sensitizes Mantle Cell Lymphoma Cells to Everolimus

2012 ◽  
Vol 48 ◽  
pp. S204
Author(s):  
L. Rosich ◽  
S. Xargay-Torrent ◽  
M. Lopez-Guerra ◽  
E. Campo ◽  
D. Colomer ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphoma Cells ◽  
Mantle Cell ◽  
Autophagy Inhibition
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