Additive and synergistic inhibition of mantle cell lymphoma cell growth by combining olaparib with ibrutinib

2018 ◽  
Vol 119 (7) ◽  
pp. 5843-5851 ◽  
Author(s):  
Adam Curtis ◽  
Jens Rueter ◽  
Shelia Rajan ◽  
Rong Zhang ◽  
Lindsay Shopland
Keyword(s):  
Cell Growth ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Synergistic Inhibition ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell

Expression of STAT3 and its phosphorylated forms in mantle cell lymphoma cell lines and tumours

2002 ◽  
Vol 199 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Raymond Lai ◽  
George Z Rassidakis ◽  
L Jeffrey Medeiros ◽  
Vasiliki Leventaki ◽  
Micheal Keating ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell

Induction of Apoptosis in Jeko-1 Mantle Cell Lymphoma Cell Line by Resveratrol: A Proteomic Analysis

2008 ◽  
Vol 7 (7) ◽  
pp. 2670-2680 ◽  
Author(s):  
Daniela Cecconi ◽  
Alberto Zamò ◽  
Alice Parisi ◽  
Elena Bianchi ◽  
Claudia Parolini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Line ◽  
Proteomic Analysis ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell ◽  
Induction Of Apoptosis

Cell Cycle Regulation by Iron: Novel Approaches to Mantle Cell Lymphoma Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2515-2515 ◽  
Author(s):  
Heather Gilbert ◽  
John Cumming ◽  
Josef T. Prchal
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Iron Chelation ◽  
Lymphoma Cell ◽  
Protein Levels ◽  
Mantle Cell

Abstract Abstract 2515 Poster Board II-492 Mantle cell lymphoma is a well defined subtype of B-cell non-Hodgkin lymphoma characterized by a translocation that juxtaposes the BCL1 gene on chromosome 11q13 (which encodes cyclin D1) next to the immunoglobulin heavy chain gene promoter on chromosome 14q32. The result is constitutive overexpression of cyclin D1 (CD1) resulting in deregulation of the cell cycle and activation of cell survival mechanisms. There are no “standard” treatments for MCL. Despite response rates to many chemotherapy regimens of 50% to 70%, the disease typically progresses after treatment, with a median survival time of approximately 3-4 years. Mantle cell lymphoma represents a small portion of malignant lymphomas, but it accounts for a disproportionately large percentage of lymphoma-related mortality. Novel therapeutic approaches are needed. In 2007, Nurtjaha-Tjendraputra described how iron chelation causes post-translational degradation of cyclin D1 via von Hippel Lindau protein-independent ubiquitinization and subsequent proteasomal degradation (1). Nurtjaha-Tjendraputra demonstrated that iron chelation inhibits cell cycle progression and induces apoptosis via proteosomal degradation of cyclin D1 in various cell lines, including breast cancer, renal carcinoma, neuroepithelioma and melanoma. Our preliminary data show similar findings in mantle cell lymphoma. To establish whether iron chelation can selectively inhibit and promote apoptosis in mantle cell derived cell lines, the human MCL cell lines Jeko-1, Mino, Granta and Hb-12; the Diffuse Large B cell lymphoma line SUDHL-6; and the Burkitt's Lymphoma lines BL-41 and DG75 were grown with media only, with two different iron chelators (deferoxamine (DFO) and deferasirox) at various concentrations (10, 20, 40, 100 and 250 μM), and with DMSO as an appropriate vehicle control. Cells were harvested at 24, 48 and 72 hours. For detection of apoptotic cells, cell-surface staining was performed with FITC-labeled anti–Annexin V antibody and PI (BD Pharmingen, San Diego, CA). Cell growth was analyzed using the Promega MTS cytotoxicity assay. CD1 protein levels were assessed using standard Western blot techniques. At 24, 48 and 72 hours of incubation with iron chelators, the mantle cell lymphoma cell lines showed significantly increased rates of apoptosis compared to the non-mantle cell lymphoma cell lines (p<0.0001 for all time points). DFO and deferasirox inhibted cell growth with an IC50 of 18 and 12 μM respectively. All of the mantle cell lines had measurable cyclin D1 levels at baseline. None of the non-mantle cell lines expressed baseline measurable cyclin D1. In the mantle cell lines, cyclin D1 protein levels were no longer apparent on western blot after 24 hours of incubation with chelation. We then added ferrous ammonium sulfate (FAS) to DFO in a 1:1 molarity ratio and to deferasirox in a 2:1 ratio, and then treated the same lymphoma cell lines with the FAS/chelator mixture and with FAS alone for 72 hours. Adding iron to the chelators completely negated all the pro-apoptotic effects that were seen with iron chelation treatment. Treating with FAS alone had no effect on cell growth or apoptosis. Iron chelation therapy with both DFO and deferasirox results in decreased cell growth, increased cellular apoptosis, and decreased cyclin D1 protein levels in vitro in mantle cell lymphoma. The cytotoxic effects are prevented by coincubation with ferrous ammonium citrate, confirming that the effects are due to iron depletion. Proposed future research includes further defining the molecular basis of iron chelation effects; studying these therapies in combination with other cancer treatments both in vitro and in vivo; and studying iron chelation therapy in mantle cell lymphoma patients. 1. Nurtjahja-Tjendraputra, E., D. Fu, et al. (2007). “Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression.” Blood109(9): 4045–54. Disclosures: No relevant conflicts of interest to declare.

Genomic imbalances and patterns of karyotypic variability in mantle-cell lymphoma cell lines

2006 ◽  
Vol 30 (8) ◽  
pp. 923-934 ◽  
Author(s):  
Jordi Camps ◽  
Itziar Salaverria ◽  
Maria J. Garcia ◽  
Esther Prat ◽  
Sílvia Beà ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Mantle Cell Lymphoma Cell ◽  
Genomic Imbalances ◽  
Karyotypic Variability ◽  
Mantle Cell

scholarly journals Characterization of a mantle cell lymphoma cell line resistant to the Chk1 inhibitor PF-00477736

Oncotarget ◽  
2015 ◽  
Vol 6 (35) ◽  
pp. 37229-37240 ◽  
Author(s):  
Valentina Restelli ◽  
Rosaria Chilà ◽  
Monica Lupi ◽  
Andrea Rinaldi ◽  
Ivo Kwee ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Line ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell ◽  
Chk1 Inhibitor

JNK is constitutively active in mantle cell lymphoma: cell cycle deregulation and polyploidy by JNK inhibitor SP600125

2009 ◽  
Vol 218 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Miao Wang ◽  
Çiğdem Atayar ◽  
Stefano Rosati ◽  
Anneke Bosga-Bouwer ◽  
Philip Kluin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell ◽  
Cell Cycle Deregulation ◽  
Constitutively Active

Combining Ibrutinib with Chk1 Inhibitors Synergistically Targets Mantle Cell Lymphoma Cell Lines

2018 ◽  
Vol 13 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Valentina Restelli ◽  
Monica Lupi ◽  
Micaela Vagni ◽  
Rosaria Chilà ◽  
Francesco Bertoni ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell

scholarly journals Characterising a human endogenous retrovirus(HERV)-derived tumour-associated antigen: enriched RNA-Seq analysis of HERV-K(HML-2) in mantle cell lymphoma cell lines

Mobile DNA ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Witold Tatkiewicz ◽  
James Dickie ◽  
Franchesca Bedford ◽  
Alexander Jones ◽  
Mark Atkin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Human Endogenous Retrovirus ◽  
Rna Seq ◽  
Tissue Specific ◽  
Mantle Cell Lymphoma Cell ◽  
Mantle Cell

Abstract Background The cell-surface attachment protein (Env) of the HERV-K(HML-2) lineage of endogenous retroviruses is a potentially attractive tumour-associated antigen for anti-cancer immunotherapy. The human genome contains around 100 integrated copies (called proviruses or loci) of the HERV-K(HML-2) virus and we argue that it is important for therapy development to know which and how many of these contribute to protein expression, and how this varies across tissues. We measured relative provirus expression in HERV-K(HML-2), using enriched RNA-Seq analysis with both short- and long-read sequencing, in three Mantle Cell Lymphoma cell lines (JVM2, Granta519 and REC1). We also confirmed expression of the Env protein in two of our cell lines using Western blotting, and analysed provirus expression data from all other relevant published studies. Results Firstly, in both our and other reanalysed studies, approximately 10% of the transcripts mapping to HERV-K(HML-2) came from Env-encoding proviruses. Secondly, in one cell line the majority of the protein expression appears to come from one provirus (12q14.1). Thirdly, we find a strong tissue-specific pattern of provirus expression. Conclusions A possible dependency of Env expression on a single provirus, combined with the earlier observation that this provirus is not present in all individuals and a general pattern of tissue-specific expression among proviruses, has serious implications for future HERV-K(HML-2)-targeted immunotherapy. Further research into HERV-K(HML-2) as a possible tumour-associated antigen in blood cancers requires a more targeted, proteome-based, screening protocol that will consider these polymorphisms within HERV-K(HML-2). We include a plan (and necessary alignments) for such work.

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