Variable Responses of MYC Translocation Positive Lymphoma Cell Lines To Different Combinations of Novel Agents: Impact of BCL2 Family Protein Expression

  title={Variable Responses of MYC Translocation Positive Lymphoma Cell Lines To Different Combinations of Novel Agents: Impact of BCL2 Family Protein Expression},
  author={Wenhan Deng and Alexandra Clipson and Hongxiang Liu and Yuanxue Huang and Rachel Dobson and Ming Wang and Peter Johnson and Ming-Qing Du},
  journal={Translational Oncology},
  pages={1147 - 1154}
Several newly developed drugs including JQ1 (BET inhibitor), ABT199 (BCL2 inhibitor), and bortezomib (proteasome inhibitor) may offer novel therapeutic strategies for aggressive diffuse large B-cell lymphoma (DLBCL). We tested these drugs together with doxorubicin in a series of combinations in 16 DLBCL cell lines including 4 ABC-DLBCL (OCI-Ly3, OCI-Ly10, SUDHL2, RIVA) and 12 GCB-DLBCL lines (OCI-Ly4, OCI-Ly18, BJAB, SUDHL4, SUDHL6, SUDHL10, DB, PR1, VAL, SC1, Karpas-231, Karpas-422). Among… Expand
The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models
Antibody-drug conjugates (ADC) are a novel way to deliver potent cytotoxic compounds to cells expressing a specific antigen. Four ADC targeting CD19, including SAR3419 (coltuximab ravtansine), haveExpand
Targeting BCL2 with venetoclax is a promising therapeutic strategy for “double-proteinexpression” lymphoma with MYC and BCL2 rearrangements
It is found that venetoclax not only disrupts the interaction between BCL2 and the pro-apoptotic protein BIM, but also leads to dephosphorylation of B CL2 and further downregulates MCL1 protein expression, probably through modulation of the protein phosphatase 2A B56α activity in Karpas231 and OCI-Ly8. Expand
Identification of PLA2G7 as a novel biomarker of diffuse large B cell lymphoma
  • Weili Zheng, Qiaochu Lin, Mohammed Awal Issah, Ziyuan Liao, Jianzhen Shen
  • Medicine
  • BMC cancer
  • 2021
PLA2G7 may represent an important diagnostic, prognostic, or therapeutic biomarker in patients with DLBCL and is found to be closely linked to tumor microenvironmental composition. Expand
Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma
It is demonstrated that CKD-581 inhibited the class I–II HDAC family via histone H3 and tubulin acetylation and induced apoptosis via poly(ADP ribose) polymerase 1 (PARP1) cleavage, suggesting that CKd-581 could be a good candidate for the treatment of DLBCL. Expand
Induction of Cross-resistance to ABCB1 Substrates in Venetoclax-resistant Human Leukemia HL60 Cells
HL60/VEN cells exhibited up-regulation of ABCB1 in addition to an alteration in apoptotic activity, and cross-resistance toABCB1 substrates was clarified, however, sensitivity to venetoclax was hardly affected by ABCB 1. Expand
Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes
A distinct mutation profile for EBV+ and EBV-negativeDLBCL is depicted and differential expression of KMT2D and MYC with potential prognostic influence is validated, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL. Expand
Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition
It is reported that histone deacetylase 6 (HDAC6) inhibition using the novel inhibitor Marbostat-100 (M-100) specifically alters protein-protein interactions in MyC-dependent cancer cells and targets MYC for proteasomal degradation, and massive apoptosis is induced in MYC-overexpressing B-cell lymphoma cells after M-100 treatment. Expand
Product Data Sheet Chemical Properties Product
Chemical Name: N,N,2-trimethyl-5-nitrobenzenesulfonamide Canonical SMILES: CC1=C(S(N(C)C)(=O)=O)C=C(N(=O)=O)C=C1 Solubility: Soluble in DMSO Storage: Store at -20°C General tips: For obtaining aExpand


The Sensitivity of Diffuse Large B-Cell Lymphoma Cell Lines to Histone Deacetylase Inhibitor-Induced Apoptosis Is Modulated by BCL-2 Family Protein Activity
The results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. Expand
ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor activity of chemotherapy, bortezomib and JQ1 in “double hit” lymphoma cells
ABT-199 was more potent than ABT-737, and is the most promising of the BH3 mimetics to date, providing a rationale for a clinical trial of these combinations in patients with relapsed DHL. Expand
Synergistic Induction of Apoptosis in High-Risk DLBCL by BCL2 Inhibition with ABT-199 Combined With Pharmacologic Loss of MCL1
A rational treatment paradigm is revealed to strip DLBCL of its protection from apoptosis and improve outcomes for high-risk patients with diffuse large B-cell lymphoma. Expand
Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma.
Bortezomib enhances the activity of chemotherapy in ABC but not GCBDLBCL, and provide a rational therapeutic approach based on genetically distinct DLBCL subtypes, are suggested. Expand
The Dual PI3K/mTOR Inhibitor PQR309 Has Synergistic Activity with Other Targeted Agents in Diffuse Large B Cell Lymphomas
Extended combination data are presented that might enhance the anti-proliferative effect of the single drug PQR309 in patients with relapsed or refractory lymphomas and an up-regulation of the PIM1 kinase after exposure to PQr309 is observed. Expand
Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib
It is demonstrated that dasatinib inhibits cell growth through G1-S blockage in five of seven DLBCL cell lines at clinically achievable concentrations and the possibility of using Syk and PLCγ2 as biomarkers to predict dAsatinib therapeutic response in prospective clinical trials is suggested. Expand
Targeting of BCL 2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL 2-and MCL 1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma
Purpose: To investigate the roles of BCL2, MCL1, and BCL-XL in the survival of diffuse large B-cell lymphoma (DLBCL). Experimental designs: Immunohistochemical analysis of 105 primary DLBCL samples,Expand
Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma
DLBCL can be divided into BCL2-dependent and MCL1-dependent subgroups with a less pronounced role left for BCL-XL, and concurrent inhibition of BCL1 with ABT-199 and HHT induced significant synthetic lethality in most B CL2-expressing DLBCL cell lines. Expand
MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies
A genetic approach, through siRNA-mediated down-regulation of AKT, MCL-1, and BCL-xL, significantly decreased cell survival, demonstrating the importance of these cell survival factors for ABT-199 resistance. Expand
MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma
MCL1 is deregulated in a significant fraction of ABC DLBCLs and contributes to therapy resistance and the data suggest that specific inhibition of MCL1 might be utilized therapeutically in a subset of DL BCLs. Expand