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2. Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma

Author

Thongon, Natthakan, Ma, Feiyang, Baran, Natalia, Lockyer, Pamela, Liu, Jintan, Jackson, Christopher, Rose, Ashley, Furudate, Ken, Wildeman, Bethany, Marchesini, Matteo, Marchica, Valentina, Storti, Paola, Todaro, Giannalisa, Ganan-Gomez, Irene, Adema, Vera, Rodriguez-Sevilla, Juan Jose, Qing, Yun, Ha, Min Jin, Fonseca, Rodrigo, Stein, Caleb, Class, Caleb, Tan, Lin, Attanasio, Sergio, Garcia-Manero, Guillermo, Giuliani, Nicola, Berrios Nolasco, David, Santoni, Andrea, Cerchione, Claudio, Bueso-Ramos, Carlos, Konopleva, Marina, Lorenzi, Philip, Takahashi, Koichi, Manasanch, Elisabet, Sammarelli, Gabriella, Kanagal-Shamanna, Rashmi, Viale, Andrea, Chesi, Marta, and Colla, Simona

Published
2024
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5. High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma

Author

Cheng, Yan, Sun, Fumou, Alapat, Daisy V., Wanchai, Visanu, Mery, David, Guo, Wancheng, Cao, Huojun, Zhu, Yuqi, Ashby, Cody, Bauer, Michael Anton, Nookaew, Intawat, Siegel, Eric R., Ying, Jun, Chen, Jin-Ran, Gai, Dongzheng, Peng, Bailu, Xu, Hongwei, Bailey, Clyde, Al Hadidi, Samer, Schinke, Carolina, Thanendrarajan, Sharmilan, Zangari, Maurizio, Chesi, Marta, Bergsagel, P. Leif, van Rhee, Frits, Janz, Siegfried, Tricot, Guido, Shaughnessy, John D., Jr., and Zhan, Fenghuang

Published
2023
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6. Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

Author

Larrayoz, Marta, Garcia-Barchino, Maria J., Celay, Jon, Etxebeste, Amaia, Jimenez, Maddalen, Perez, Cristina, Ordoñez, Raquel, Cobaleda, Cesar, Botta, Cirino, Fresquet, Vicente, Roa, Sergio, Goicoechea, Ibai, Maia, Catarina, Lasaga, Miren, Chesi, Marta, Bergsagel, P. Leif, Larrayoz, Maria J., Calasanz, Maria J., Campos-Sanchez, Elena, Martinez-Cano, Jorge, Panizo, Carlos, Rodriguez-Otero, Paula, Vicent, Silvestre, Roncador, Giovanna, Gonzalez, Patricia, Takahashi, Satoru, Katz, Samuel G., Walensky, Loren D., Ruppert, Shannon M., Lasater, Elisabeth A., Amann, Maria, Lozano, Teresa, Llopiz, Diana, Sarobe, Pablo, Lasarte, Juan J., Planell, Nuria, Gomez-Cabrero, David, Kudryashova, Olga, Kurilovich, Anna, Revuelta, Maria V., Cerchietti, Leandro, Agirre, Xabier, San Miguel, Jesus, Paiva, Bruno, Prosper, Felipe, and Martinez-Climent, Jose A.

Published
2023
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7. CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma

Author

Yao, Yao, Ng, Jessica Fong, Park, Woojun Daniel, Samur, Mehmet, Morelli, Eugenio, Encinas Mayoral, Jessica, Chyra, Zuzana, Xu, Yan, Derebail, Sanika, Epstein, Charles, Nabet, Behnam, Chesi, Marta, Gray, Nathanael S., Young, Richard A., Kwiatkowski, Nicholas, Mitsiades, Constantine, Anderson, Kenneth C., Lin, Charles Y., Munshi, Nikhil C., and Fulciniti, Mariateresa

Published
2023
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8. Microbiome Modulation Uncouples Efficacy and Toxicity Induced by Programmed Death-1/Programmed Death-Ligand1 Blockade

Author

Cogrossi, Laura Lucia, primary, Zordan, Paola, additional, Grioni, Matteo, additional, Tosi, Anna, additional, Rizzo, Nathalie, additional, Policastro, Anna, additional, Mattorre, Benedetta, additional, Lorenzoni, Marco, additional, Meregalli, Greta, additional, Sisti, Sofia, additional, Sanvito, Francesca, additional, Chesi, Marta, additional, Bergsagel, Leif, additional, Clementi, Nicola, additional, Rosato, Antonio, additional, and Bellone, Matteo, additional

Published
2024
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9. Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice

Author

Wen, Zhi, Rajagopalan, Adhithi, Flietner, Evan D., Yun, Grant, Chesi, Marta, Furumo, Quinlan, Burns, Robert T., Papadas, Athanasios, Ranheim, Erik A., Pagenkopf, Adam C., Morrow, Zachary T., Finn, Remington, Zhou, Yun, Li, Shuyi, You, Xiaona, Jensen, Jeffrey, Yu, Mei, Cicala, Alexander, Menting, James, Mitsiades, Constantine S., Callander, Natalie S., Bergsagel, P. Leif, Wang, Demin, Asimakopoulos, Fotis, and Zhang, Jing

Published
2021
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10. Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma

Author

Ghobrial, Irene M., primary, Gormley, Nicole, additional, Kumar, Shaji K., additional, Mateos, Maria-Victoria, additional, Bergsagel, P. Leif, additional, Chesi, Marta, additional, Dhodapkar, Madhav V., additional, Dispenzieri, Angela, additional, Fonseca, Rafael, additional, Getz, Gad, additional, Kastritis, Efstathios, additional, Kristinsson, Sigurdur Y., additional, Martinez-Climent, Jose Angel, additional, Manier, Salomon, additional, Marinac, Catherine R., additional, Maura, Francesco, additional, Morgan, Gareth J., additional, Davies, Faith E., additional, Nadeem, Omar, additional, Nuvolone, Mario, additional, Paiva, Bruno, additional, O’Donnell, Elizabeth, additional, Prosper, Felipe, additional, Shah, Urvi A., additional, Sklavenitis-Pistofidis, Romanos, additional, Sperling, Adam S., additional, Vassiliou, George S., additional, Munshi, Nikhil C., additional, Castle, Philip E., additional, Anderson, Kenneth C., additional, and San Miguel, Jesus F., additional

Published
2024
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11. Genomic Classification and Individualized Prognosis in Multiple Myeloma

Author

Maura, Francesco, primary, Rajanna, Arjun Raj, additional, Ziccheddu, Bachisio, additional, Poos, Alexandra M., additional, Derkach, Andriy, additional, Maclachlan, Kylee, additional, Durante, Michael, additional, Diamond, Benjamin, additional, Papadimitriou, Marios, additional, Davies, Faith, additional, Boyle, Eileen M., additional, Walker, Brian, additional, Hultcrantz, Malin, additional, Silva, Ariosto, additional, Hampton, Oliver, additional, Teer, Jamie K., additional, Siegel, Erin M., additional, Bolli, Niccolò, additional, Jackson, Graham H., additional, Kaiser, Martin, additional, Pawlyn, Charlotte, additional, Cook, Gordon, additional, Kazandjian, Dickran, additional, Stein, Caleb, additional, Chesi, Marta, additional, Bergsagel, Leif, additional, Mai, Elias K., additional, Goldschmidt, Hartmut, additional, Weisel, Katja C., additional, Fenk, Roland, additional, Raab, Marc S., additional, Van Rhee, Fritz, additional, Usmani, Saad, additional, Shain, Kenneth H., additional, Weinhold, Niels, additional, Morgan, Gareth, additional, and Landgren, Ola, additional

Published
2024
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12. Supplementary Table 1 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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13. Supplementary Data 4 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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14. Supplementary Data 3 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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15. Data from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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16. Supplementary Table 2 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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17. Supplementary Data 1 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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18. Supplementary Data 2 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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19. Supplementary Data 5 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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20. Supplementary Figures S1-S11 from Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., primary, Meermeier, Erin W., primary, Riggs, Daniel L., primary, Shi, Chang-Xin, primary, Zhu, Yuan Xiao, primary, Sharik, Meaghen E., primary, Du, Megan T., primary, Abrego Rocha, Leslie D., primary, Garbitt, Victoria M., primary, Stein, Caleb K., primary, Petit, Joachim L., primary, Meurice, Nathalie, primary, Tafoya Alvarado, Yuliza, primary, Fonseca, Rodrigo, primary, Todd, Kennedi T., primary, Brown, Sochilt, primary, Hammond, Zachery J., primary, Cuc, Nicklus H., primary, Wittenberg, Courtney, primary, Herzog, Camille, primary, Roschke, Anna V., primary, Demchenko, Yulia N., primary, Chen, Wei-dong D., primary, Li, Peng, primary, Liao, Wei, primary, Leonard, Warren J., primary, Lonial, Sagar, primary, Bahlis, Nizar J., primary, Neri, Paola, primary, Boise, Lawrence H., primary, Chesi, Marta, primary, and Bergsagel, P. Leif, primary

Published
2024
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21. A High-Fiber Dietary Intervention (NUTRIVENTION) in Precursor Plasma Cell Disorders Improves Disease Biomarkers and Delays Progression to Myeloma

Author

Shah, Urvi, primary, Cogrossi, Laura Lucia, additional, Derkach, Andriy, additional, Castro, Francesca, additional, Fei, Teng, additional, DeWolf, Susan, additional, Garces, Juan-Jose, additional, Policastro, Anna, additional, Grioni, Matteo, additional, Sisti, Sofia, additional, Blaslov, Jenna, additional, Adintori, Peter, additional, Hosszu, Kinga K., additional, McAvoy, Devin, additional, Baichoo, Mirae, additional, Cross, Justin R., additional, Anuraj, Aishwarya, additional, Pohl, Charlotte, additional, Ramos, Ruben, additional, Paredes, Jenny, additional, Gipson, Brianna, additional, Maclachlan, Kylee, additional, Gradissimo, Ana, additional, Boiocchi, Leonardo, additional, Koche, Richard, additional, Chaligne, Ronan, additional, Block, Torin, additional, Korde, Neha, additional, Tan, Carlyn Rose, additional, Hultcrantz, Malin, additional, Hassoun, Hani, additional, Shah, Gunjan, additional, Scordo, Michael, additional, Lahoud, Oscar B., additional, Chung, David J., additional, Landau, Heather J., additional, Peled, Jonathan U., additional, Clementi, Nicola, additional, Chesi, Marta, additional, Bergsagel, Peter, additional, Mailankody, Sham, additional, Pollak, Michael, additional, D'Souza, Anita, additional, Landgren, Ola, additional, Chimonas, Susan, additional, Giralt, Sergio A., additional, Usmani, Saad, additional, Iyengar, Neil M., additional, Lesokhin, Alexander, additional, Bellone, Matteo, additional, and van den Brink, Marcel R.M., additional

Published
2024
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23. MYC dysregulation in the progression of multiple myeloma

Author

Misund, Kristine, Keane, Niamh, Stein, Caleb K., Asmann, Yan W., Day, Grady, Welsh, Seth, Van Wier, Scott A., Riggs, Daniel L., Ahmann, Greg, Chesi, Marta, Viswanatha, David S., Kumar, Shaji K., Dispenzieri, Angela, Gonzalez-Calle, Veronica, Kyle, Robert A., O’Dwyer, Michael, Rajkumar, S. Vincent, Kortüm, K. Martin, Keats, J. Jonathan, Fonseca, Rafael, Stewart, A. Keith, Kuehl, W. Michael, Braggio, Esteban, and Bergsagel, P. Leif

Published
2020
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25. TIM-3+ CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies.

Author

Minnie, Simone A., Waltner, Olivia G., Zhang, Ping, Takahashi, Shuichiro, Nemychenkov, Nicole S., Ensbey, Kathleen S., Schmidt, Christine R., Legg, Samuel R. W., Comstock, Melissa, Boiko, Julie R., Nelson, Ethan, Bhise, Shruti S., Wilkens, Alec B., Koyama, Motoko, Dhodapkar, Madhav V., Chesi, Marta, Riddell, Stanley R., Green, Damian J., Spencer, Andrew, and Furlan, Scott N.

Subjects
T-cell exhaustion, HEMATOLOGIC malignancies, BONE marrow cancer, CHIMERIC antigen receptors, PHENOTYPES
Abstract

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (TPHEX), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ+ TPHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ+ TPHEX. We also observed IFN-γ+ TPHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19+ leukemia cells. An IFN-γ+ TPHEX gene signature was recapitulated in TEX cells from human cancers, including myeloma and lymphoma. Here, we characterize a TEX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional TEX found in chronic viral infections. Thus, IFN-γ+ TPHEX represent a potential target for immunotherapy of blood cancers. Editor's Summary: Chronic antigen stimulation can drive CD8 T cell exhaustion and dysfunction among multiple T cell subsets. Using a murine myeloma model, Minnie et al. characterized a terminally exhausted CD8 T cell subset in the bone marrow tumor microenvironment that expressed not only transcription and epigenetic factors associated with exhaustion but also effector molecules, including IFN-γ, granzymes, and perforin. This subset, IFN-γ+ TPHEX (IFN-γ–secreting, phenotypically exhausted T cells), could kill myeloma cells, and IFN-γ+ TPHEX differentiated from CD19-targeted chimeric antigen receptor T cells could kill CD19+ tumor cells. An analogous IFN-γ+ TPHEX subset was also detected in patients with myeloma and lymphoma. Together, these findings suggest that IFN-γ+ TPHEX have dysfunctional features but retain functionality, facilitating antitumor responses. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Published
2024
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26. 1200 Leveraging the immunocompetent Vk*MYChCRBNmodel of multiple myeloma to determine and overcome T cell engager antibody resistance mechanisms

Author

Meermeier, Erin W, primary, Stein, Caleb, additional, Sharik, Meaghen, additional, Du, Megan, additional, Shi, Chang-Xin, additional, Zhu, Yuan Xiao, additional, Abayasiriwardana, Keith, additional, Fisher, Timothy, additional, Baaten, Bas, additional, Bezman, Natalie, additional, Bompiani-Myers, Kristin, additional, Leif Bergsagel, P, additional, and Chesi, Marta, additional

Published
2023
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28. Bone marrow transplantation generates T cell-dependent control of myeloma in mice

Author

Vuckovic, Slavica, Minnie, Simone A., Smith, David, Gartlan, Kate H., Watkins, Thomas S., Markey, Kate A., Mukhopadhyay, Pamela, Guillerey, Camille, Kuns, Rachel D., Locke, Kelly R., Pritchard, Antonia L., Johansson, Peter A., Varelias, Antiopi, Zhang, Ping, Huntington, Nicholas D., Waddell, Nicola, Chesi, Marta, Miles, John J., Smyth, Mark J., and Hill, Geoffrey R.

Subjects
T cells -- Research, Bone marrow transplantation -- Usage, Multiple myeloma -- Control, Laboratory rats -- Health aspects, Health care industry
Abstract

Transplantation with autologous hematopoietic progenitors remains an important consolidation treatment for patients with multiple myeloma (MM) and is thought to prolong the disease plateau phase by providing intensive cytoreduction. However, transplantation induces inflammation in the context of profound lymphodepletion that may cause hitherto unexpected immunological effects. We developed preclinical models of bone marrow transplantation (BMT) for MM using Vk*MYC myeloma-bearing recipient mice and donor mice that were myeloma naive or myeloma experienced to simulate autologous transplantation. Surprisingly, we demonstrated broad induction of T cell-dependent myeloma control, most efficiently from memory T cells within myeloma-experienced grafts, but also through priming of naive T cells after BMT. [CD8.sup.+] T cells from mice with controlled myeloma had a distinct T cell receptor (TCR) repertoire and higher clonotype overlap relative to myeloma-free BMT recipients. Furthermore, T cell-dependent myeloma control could be adoptively transferred to secondary recipients and was myeloma cell clone specific. Interestingly, donor-derived IL-17A acted directly on myeloma cells expressing the IL-17 receptor to induce a transcriptional landscape that promoted tumor growth and immune escape. Conversely, donor IFN-[gamma] secretion and signaling were critical to protective immunity and were profoundly augmented by CD137 agonists. These data provide new insights into the mechanisms of action of transplantation in myeloma and provide rational approaches to improving clinical outcomes., IntroductionMultiple myeloma (MM) is a bone marrow-based (BM-based) plasma cell neoplasm that often evolves from a premalignant stage, known as monoclonal gammopathy of undetermined significance (MGUS), to present with characteristic [...]

Published
2019
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30. Role of Pirh2 in mediating the regulation of p53 and c-Myc.

Author

Hakem, Anne, Bohgaki, Miyuki, Lemmers, Bénédicte, Tai, Elisabeth, Salmena, Leonardo, Matysiak-Zablocki, Elzbieta, Jung, Yong-Sam, Karaskova, Jana, Kaustov, Lilia, Duan, Shili, Madore, Jason, Boutros, Paul, Sheng, Yi, Chesi, Marta, Bergsagel, P Leif, Perez-Ordonez, Bayardo, Mes-Masson, Anne-Marie, Penn, Linda, Squire, Jeremy, Chen, Xinbin, Jurisica, Igor, Arrowsmith, Cheryl, Sanchez, Otto, Benchimol, Samuel, and Hakem, Razqallah

Subjects
Animals, Mice, Inbred C57BL, Humans, Mice, Neoplasms, Cell Transformation, Neoplastic, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-myc, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Radiation Tolerance, Tumor Suppressor Protein p53, Ubiquitination, Kaplan-Meier Estimate, HEK293 Cells, Proteolysis, Inbred C57BL, Cell Transformation, Neoplastic, Gene Expression Regulation, Genes, Tumor Suppressor, Genetics, Developmental Biology
Abstract

Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2(-/-) mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor.

Published
2011

31. Transcriptional heterogeneity overcomes super-enhancer disrupting drug combinations in multiple myeloma

Author

Welsh, Seth J., primary, Barwick, Benjamin G., additional, Meermeier, Erin W., additional, Riggs, Daniel L., additional, Shi, Chang-Xin, additional, Zhu, Yuan Xiao, additional, Sharik, Meaghen E., additional, Du, Megan T., additional, Rocha, Leslie D Abrego., additional, Garbitt, Victoria M., additional, Stein, Caleb K., additional, Petit, Joachim L., additional, Meurice, Nathalie, additional, Tafoya Alvarado, Yuliza, additional, Fonseca, Rodrigo, additional, Todd, Kennedi T., additional, Brown, Sochilt, additional, Hammond, Zachary J., additional, Cuc, Nicklus H., additional, Wittenberg, Courtney, additional, Herzog, Camille, additional, Roschke, Anna V., additional, Demchenko, Yulia N., additional, Chen, Wei-dong D., additional, Li, Peng, additional, Liao, Wei, additional, Leonard, Warren J., additional, Lonial, Sagar, additional, Bahlis, Nizar J., additional, Neri, Paola, additional, Boise, Lawrence H., additional, Chesi, Marta, additional, and Bergsagel, P. Leif, additional

Published
2023
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36. OA-01 Exploiting microbiota commensals to potentiate immunotherapy and delay multiple myeloma evolution

Author

Cogrossi, Laura Lucia, primary, Ferrarese, Roberto, additional, Grioni, Matteo, additional, Zordan, Paola, additional, Mattorre, Benedetta, additional, Lorenzoni, Marco, additional, Meregalli, Greta, additional, Policastro, Anna, additional, Sisti, Sofia, additional, Brevi, Arianna, additional, Chesi, Marta, additional, Bergsagel, Leif, additional, Clementi, Nicola, additional, Mancini, Nicasio, additional, and Matteo, Bellone, additional

Published
2023
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37. S185: TARGETING DNA2 OVERCOMES METABOLIC REPROGRAMMING IN 1Q21 MULTIPLE MYELOMA

Author

Thongon, Natthakan, primary, MA, Feiyang, additional, Lockyer, Pamela, additional, Baran, Natalia, additional, Liu, Jintan, additional, Class, Caleb, additional, Tan, Lin, additional, Storti, Paola, additional, Marchica, Valentina, additional, Ganan-Gomez, Irene, additional, Wildeman, Bethany, additional, Adema, Vera, additional, Lorenzi, Philip, additional, Fonseca, Rodrigo, additional, Chesi, Marta, additional, Manasanch, Elisabeth, additional, Viale, Andrea, additional, and Colla, Simona, additional

Published
2023
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38. The Vk*MYC Mouse Model recapitulates human multiple myeloma evolution and genomic diversity

Author

Maura, Francesco, primary, Coffey, David G., additional, Stein, Caleb K, additional, Braggio, Esteban, additional, Ziccheddu, Bachisio, additional, Sharik, Meaghen E, additional, Du, Megan, additional, Alvarado, Yuliza Tofaya, additional, Shi, Chang-Xin, additional, Zhu, Yuan Xiao, additional, Meermeier, Erin W., additional, Morgan, Gareth J., additional, Landgren, Ola, additional, Leif Bergsagel, P., additional, and Chesi, Marta, additional

Published
2023
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41. Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression

Author

Kawano, Yawara, Zavidij, Oksana, Park, Jihye, Moschetta, Michele, Kokubun, Katsutoshi, Mouhieddine, Tarek H., Manier, Salomon, Mishima, Yuji, Murakami, Naoka, Bustoros, Mark, Pistofidis, Romanos Sklavenitis, Reidy, Mairead, Shen, Yu.J., Rahmat, Mahshid, Lukyanchykov, Pavlo, Karreci, Esilida Sula, Tsukamoto, Shokichi, Shi, Jiantao, Takagi, Satoshi, Huynh, Daisy, Sacco, Antonio, Tai, Yu-Tzu, Chesi, Marta, Bergsagel, P. Leif, Roccaro, Aldo M., Azzi, Jamil, and Ghobrial, Irene M.

Subjects
Cancer research, Multiple myeloma -- Development and progression, Immunotherapy -- Research, Interferon -- Physiological aspects -- Health aspects, Cytokine receptors -- Health aspects, T cells -- Physiological aspects -- Health aspects, Health care industry
Abstract

Despite significant advances in the treatment of multiple myeloma (MM), most patients succumb to disease progression. One of the major immunosuppressive mechanisms that is believed to play a role in myeloma progression is the expansion of regulatory T cells (Tregs). In this study, we demonstrate that myeloma cells drive Treg expansion and activation by secreting type 1 interferon (IFN). Blocking IFN [alpha] and [beta] receptor 1 (IFNAR1) on Tregs significantly decreases both myeloma-associated Treg immunosuppressive function and myeloma progression. Using syngeneic transplantable murine myeloma models and bone marrow (BM) aspirates of MM patients, we found that Tregs were expanded and activated in the BM microenvironment at early stages of myeloma development. Selective depletion of Tregs led to a complete remission and prolonged survival in mice injected with myeloma cells. Further analysis of the interaction between myeloma cells and Tregs using gene sequencing and enrichment analysis uncovered a feedback loop, wherein myeloma-cell-secreted type 1 IFN induced proliferation and expansion of Tregs. By using IFNAR1-blocking antibody treatment and IFNAR1-knockout Tregs, we demonstrated a significant decrease in myeloma-associated Treg proliferation, which was associated with longer survival of myeloma-injected mice. Our results thus suggest that blocking type 1 IFN signaling represents a potential strategy to target immunosuppressive Treg function in MM., Introduction Immunotherapy has shown promising results in clinical trials against both solid (1) and hematological malignancies (2), such as Hodgkin lymphoma (3). Even though targeting the immune microenvironment can lead [...]

Published
2018
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42. Supplemental Tables 1 - 2, Figures 1 - 3 from Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

Author

Jensen, Jeffrey Lee, primary, Rakhmilevich, Alexander, primary, Heninger, Erika, primary, Broman, Aimee Teo, primary, Hope, Chelsea, primary, Phan, Funita, primary, Miyamoto, Shigeki, primary, Maroulakou, Ioanna, primary, Callander, Natalie, primary, Hematti, Peiman, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Sondel, Paul, primary, and Asimakopoulos, Fotis, primary

Published
2023
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43. Data from The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma

Author

Le Moigne, Ronan, primary, Aftab, Blake T., primary, Djakovic, Stevan, primary, Dhimolea, Eugen, primary, Valle, Eduardo, primary, Murnane, Megan, primary, King, Emily M., primary, Soriano, Ferdie, primary, Menon, Mary-Kamala, primary, Wu, Zhi Yong, primary, Wong, Stephen T., primary, Lee, Grace J., primary, Yao, Bing, primary, Wiita, Arun P., primary, Lam, Christine, primary, Rice, Julie, primary, Wang, Jinhai, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Kraus, Marianne, primary, Driessen, Christoph, primary, Kiss Von Soly, Szerenke, primary, Yakes, F. Michael, primary, Wustrow, David, primary, Shawver, Laura, primary, Zhou, Han-Jie, primary, Martin, Thomas G., primary, Wolf, Jeffrey L., primary, Mitsiades, Constantine S., primary, Anderson, Daniel J., primary, and Rolfe, Mark, primary

Published
2023
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44. Supplementary Data from The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma

Author

Le Moigne, Ronan, primary, Aftab, Blake T., primary, Djakovic, Stevan, primary, Dhimolea, Eugen, primary, Valle, Eduardo, primary, Murnane, Megan, primary, King, Emily M., primary, Soriano, Ferdie, primary, Menon, Mary-Kamala, primary, Wu, Zhi Yong, primary, Wong, Stephen T., primary, Lee, Grace J., primary, Yao, Bing, primary, Wiita, Arun P., primary, Lam, Christine, primary, Rice, Julie, primary, Wang, Jinhai, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Kraus, Marianne, primary, Driessen, Christoph, primary, Kiss Von Soly, Szerenke, primary, Yakes, F. Michael, primary, Wustrow, David, primary, Shawver, Laura, primary, Zhou, Han-Jie, primary, Martin, Thomas G., primary, Wolf, Jeffrey L., primary, Mitsiades, Constantine S., primary, Anderson, Daniel J., primary, and Rolfe, Mark, primary

Published
2023
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45. Data from Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

Author

Jensen, Jeffrey Lee, primary, Rakhmilevich, Alexander, primary, Heninger, Erika, primary, Broman, Aimee Teo, primary, Hope, Chelsea, primary, Phan, Funita, primary, Miyamoto, Shigeki, primary, Maroulakou, Ioanna, primary, Callander, Natalie, primary, Hematti, Peiman, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Sondel, Paul, primary, and Asimakopoulos, Fotis, primary

Published
2023
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48. Supplementary Figure Legends from Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients

Author

Bianco, Mimma, primary, Gasparri, Anna Maria, primary, Colombo, Barbara, primary, Curnis, Flavio, primary, Girlanda, Stefania, primary, Ponzoni, Maurilio, primary, Bertilaccio, Maria Teresa Sabrina, primary, Calcinotto, Arianna, primary, Sacchi, Angelina, primary, Ferrero, Elisabetta, primary, Ferrarini, Marina, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Bellone, Matteo, primary, Tonon, Giovanni, primary, Ciceri, Fabio, primary, Marcatti, Magda, primary, Caligaris-Cappio, Federico, primary, and Corti, Angelo, primary

Published
2023
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49. Data from Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients

Author

Bianco, Mimma, primary, Gasparri, Anna Maria, primary, Colombo, Barbara, primary, Curnis, Flavio, primary, Girlanda, Stefania, primary, Ponzoni, Maurilio, primary, Bertilaccio, Maria Teresa Sabrina, primary, Calcinotto, Arianna, primary, Sacchi, Angelina, primary, Ferrero, Elisabetta, primary, Ferrarini, Marina, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Bellone, Matteo, primary, Tonon, Giovanni, primary, Ciceri, Fabio, primary, Marcatti, Magda, primary, Caligaris-Cappio, Federico, primary, and Corti, Angelo, primary

Published
2023
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50. Supplementary Figures S1-S5 from Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients

Author

Bianco, Mimma, primary, Gasparri, Anna Maria, primary, Colombo, Barbara, primary, Curnis, Flavio, primary, Girlanda, Stefania, primary, Ponzoni, Maurilio, primary, Bertilaccio, Maria Teresa Sabrina, primary, Calcinotto, Arianna, primary, Sacchi, Angelina, primary, Ferrero, Elisabetta, primary, Ferrarini, Marina, primary, Chesi, Marta, primary, Bergsagel, P. Leif, primary, Bellone, Matteo, primary, Tonon, Giovanni, primary, Ciceri, Fabio, primary, Marcatti, Magda, primary, Caligaris-Cappio, Federico, primary, and Corti, Angelo, primary

Published
2023
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