Article
Parasitology
Desmond O. Agwunobi, Tongxuan Wang, Meng Zhang, Tianhong Wang, Qingying Jia, Miao Zhang, Xinyue Shi, Zhijun Yu, Jingze Liu
Summary: In this study, genes of hsp70 and hsp90 cDNA were cloned and characterized from the tick Dermacentor silvarum, and their functions in cold stress were evaluated. Results showed that Dshsp70 and Dshsp90 play essential roles in the low-temperature adaptation of ticks. This study contributes to understanding the survival and acclimatization of overwintering ticks.
PARASITES & VECTORS
(2021)
Article
Biochemistry & Molecular Biology
Tanya Ju-Ngam, Nichanun McMillan, Mamoru Yoshimizu, Hisae Kasai, Ratree Wongpanya, Prapansak Srisapoome
Summary: This research conducted molecular characterization and biofunctional analyses of Hsp40 and Hsp90 genes in giant river prawns under various stress conditions. The highest similarity scores of these genes were found with crustaceans. Expression patterns of Mr-hsp40 and Mr-hsp90 were different under Aeromonas hydrophila challenge and heat-cold shock conditions, highlighting their significant roles in stress responses.
Article
Immunology
Marko Sustic, Maja Cokaric Brdovcak, Berislav Lisnic, Jelena Materljan, Vanda Juranic Lisnic, Carmen Rozmanic, Daniela Indenbirken, Lea Hirsl, Dirk H. Busch, Ilija Brizic, Astrid Krmpotic, Stipan Jonjic
Summary: CMV vectors have the potential to induce strong immune responses, with RAE-1 gamma MCMV showing enhanced immunoprotection against bacterial and tumor challenges. The phenotypic and functional characteristics of memory CD8 T cells induced by RAE-1 gamma MCMV were distinct compared to control vectors, with differences in cytokine production and cytotoxic potential. Adoptive transfer of cells primed with RAE-1 gamma MCMV led to efficient rejection of established tumors, highlighting the importance of latent infection and cell numbers in enhancing anti-tumor responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Assaf Gottlieb, Hoai Phuong T. Pham, John William Lindsey
Summary: This study presents a method to stimulate T lymphocytes in multiple sclerosis patients and controls using non-suppressive brain homogenate. The results suggest that the brain-responding cells from MS patients may be pathogenic based on mRNA expression and their T-cell receptor repertoire shows minimal overlap with virus antigens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Lourdes Gimeno, Isabel Gonzalez-Lozano, Maria F. Soto-Ramirez, Maria V. Martinez-Sanchez, Pedro Lopez-Cubillana, Jose L. Fuster, Jeronimo Martinez-Garcia, Jorge Martinez-Escribano, Jose A. Campillo, Eduardo Pons-Fuster, Belen Ferri, Alicia Lopez-Abad, Manuel Muro, Alfredo Minguela
Summary: The study found that the M/T dimorphism at position -21 of the HLA-B leader peptide is associated with survival and CD226 expression in cancer patients, with higher expression in patients with more methionines. CD8(+) T lymphocytes from healthy donors with -21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation.
Article
Multidisciplinary Sciences
Laura Tarnawski, Vladimir S. Shavva, Eric J. Kort, Zhengbing Zhuge, Ingrid Nilsson, Alessandro L. Gallina, David Martinez-Enguita, Benjamin Heller Sahlgren, Matthew Weiland, April S. Caravaca, Staffan Schmidt, Ping Chen, Katarina Abbas, Fu-Hua Wang, Osman Ahmed, Michael Eberhardson, Anna Farnert, Eddie Weitzberg, Mika Gustafsson, Jan Kehr, Stephen G. Malin, Henrik Hult, Mattias Carlstrom, Stefan Jovinge, Peder S. Olofsson
Summary: Endothelial dysfunction and impaired vasodilation are associated with adverse cardiovascular events. T lymphocytes expressing ChAT regulate vasodilation and play a role in the cholinergic antiinflammatory pathway. ChAT mRNA expression in human T cells is induced through the PI3K signaling cascade and regulated by REST-mediated methylation and up-regulation by GATA3. Functional experiments demonstrate that T cell-derived ACh promotes endothelial nitric oxide-synthase activity, vasorelaxation, and barrier integrity. Additionally, the frequency of ChAT(+)CD4(+) T cells in blood correlates with survival in patients with severe circulatory failure. These findings provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Marija Radmilo, Sanda Pavelin, Igor Vujovic, Josko Soda, Maja Rogic Vidakovic
Summary: The aim of this retrospective study was to compare the immunophenotyping of T-lymphocytes, B-lymphocytes, and natural killer cells before the administration of the first and second dose of ocrelizumab in multiple sclerosis patients. The study found no significant decrease in serum albumin and globulins before the second dose of ocrelizumab. A decrease in the number of T-lymphocytes was observed before the second dose, but without statistical significance. Significant depletion was observed in median CD19+ B-lymphocytes before the intake of the second dose, confirming the primary action of ocrelizumab on the B cell lineage.
Article
Oncology
Marta Gascon-Ruiz, Ariel Ramirez-Labrada, Rodrigo Lastra, Luis Martinez-Lostao, J. Ramon Pano-Pardo, Andrea Sesma, Maria Zapata-Garcia, Alba Moratiel, Elisa Quilez, Irene Torres-Ramon, Alfonso Yubero, Maria Pilar Domingo, Patricia Esteban, Eva M. Galvez, Julian Pardo, Dolores Isla
Summary: Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. This study aimed to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. The results showed that a subset of circulating CD56+CD16-PD-1+ NK cells have a good predictive ability, providing valuable information for precision medicine protocols.
Review
Biochemistry & Molecular Biology
Siarhei A. Dabravolski, Vasily N. Sukhorukov, Vladislav A. Kalmykov, Nikolay A. Orekhov, Andrey V. Grechko, Alexander N. Orekhov
Summary: Cardiovascular diseases are a major cause of death worldwide, with molecular chaperones like HSP90 playing a crucial role in heart protection and aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Aotong Zhang, Mingfeng Li, Yanjuan Wang, Ying Xiong, Tianjiao Zhu, Xin Qi, Jing Li
Summary: This study found that the new compound PNSA has low toxicity to lymphocytes and does not significantly affect the populations of CD3+, CD4+, and CD8+ T lymphocytes. It directly enhances the killing capacities of CD8+ T and CD3+CD25- cells to CT26 cells, while not affecting CD3+ cells due to the increase of Treg cells. Additionally, PNSA pretreatment of tumor cells increases sensitivity to CD8+ T cells by degrading Hsp90 client proteins and decreasing PD-L1 expression. In in vivo experiments, PNSA inhibits colon adenocarcinoma and increases CD8 T cell infiltration in tumor tissues. These findings suggest that PNSA can improve the immune function of lytic T cells and enhance its anticancer effect, providing a better foundation for the development of PNSA as an anticancer drug in the future.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ruben Osuna-Gomez, Ivan Castellvi, Maria Mulet, Ma Angels Ortiz, Douglas E. Brough, Helen Sabzevari, Roshanak T. Semnani, Silvia Vidal
Summary: This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. The study found significantly lower plasma IL-35 concentrations in SSc patients, and the levels of IL-35 showed a negative correlation with TGF-beta and IL-17. Flow cytometry analysis revealed higher levels of IL-35 receptor expression on monocytes and lower levels on CD8+ T cells in SSc patients. The addition of recombinant IL-35 reduced the percentage of IL-17+CD4+ T cells and increased the percentage of IL-35+CD4+ T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Enzo M. Scutigliani, Yongxin Liang, Marloes IJff, Hans Rodermond, Xionge Mei, Miriam P. Korver, Vaneesha S. Orie, Ron A. Hoebe, Daisy Picavet, Arlene Oei, Roland Kanaar, Przemek M. Krawczyk
Summary: Summary Hyperthermia can improve the effects of radio- and chemotherapy, but its efficacy is limited by the heat stress response (HSR). In this study, we evaluated the HSP90 inhibitor ganetespib in promoting the effects of radiotherapy or cisplatin combined with hyperthermia. Our results showed that ganetespib could enhance the efficacy of hyperthermia when combined with radiation.
Review
Biology
Xun Fu, Jiang Liu, Xin Yan, Michael E. DiSanto, Xinhua Zhang
Summary: Prostate cancer is the second most common cancer in aging men globally, but its exact pathogenesis is not fully understood. The heat shock protein (HSP) family plays a significant role in promoting tumor growth and protecting cancer cells from death. HSP molecules are closely involved in important biological processes such as cell differentiation, epithelial-mesenchymal transition, and fibrosis. Agents and inhibitors targeting the critical structure of HSP molecules have been developed for their potent antitumor effects. However, only a small number of them have been clinically tested. Further clinical studies are needed to establish the relationship between HSP70 family, HSP90 molecule, and prostate cancer treatment.
Article
Oncology
Elin Bernson, Oisin Huhn, Veronika Karlsson, Delia Hawkes, Maria Lycke, Valentina Cazzetta, Joanna Mikulak, James Hall, Anna M. Piskorz, Rosalba Portuesi, Domenico Vitobello, Barbara Fiamengo, Gabriele Siesto, Amir Horowitz, Hormas Ghadially, Domenico Mavilio, James D. Brenton, Karin Sundfeldt, Francesco Colucci
Summary: Ovarian cancer, the deadliest among gynecological cancers, requires new treatment options. Immunotherapy shows great potential but has not yet been successful for most ovarian cancer patients. By studying lymphocytes in high-grade serous ovarian cancer patients, we found the presence of natural killer cells and T cells in primary tumors and ascites. These cells express tissue-resident markers and the inhibitory receptor, NKG2A, and can kill ovarian cancer cells. In summary, we report a functional subset of lymphocytes that may be targeted in future immunotherapeutic approaches.
Review
Biochemistry & Molecular Biology
Stefan Tukaj, Krzysztof Sitko
Summary: Over a hundred different autoimmune diseases have been described to date, affecting various organs including the skin. The loss of immune tolerance in autoimmune diseases leads to chronic inflammation and tissue damage. Current treatments focus on immunosuppression but may cause serious adverse effects. Heat shock proteins Hsp90 and Hsp70 have been identified as potential therapeutic targets for autoimmune skin diseases.
Article
Hematology
Tomasz Sewastianik, Juerg R. Straubhaar, Jian-Jun Zhao, Mehmet K. Samur, Keith Adler, Helen E. Tanton, Vignesh Shanmugam, Omar Nadeem, Peter S. Dennis, Vinodh Pillai, Jianli Wang, Meng Jiang, Jianhong Lin, Ying Huang, Daniel Brooks, Mary Bouxsein, David M. Dorfman, Geraldine S. Pinkus, Davide F. Robbiani, Irene M. Ghobrial, Bogdan Budnik, Petr Jarolim, Nikhil C. Munshi, Kenneth C. Anderson, Ruben D. Carrasco
Summary: The deletion of miR-15a/16-1 cluster in murine GC B cells induces moderate but widespread molecular and functional changes, leading to the development of mature B-cell neoplasms resembling human extramedullary plasmacytoma and lymphoma. The low expression levels of miR-15a/16 in human primary EP, primarily associated with del(13q) loss, highlights the tumor-suppressor role of this cluster in plasma cell and B-cell malignancies.
Article
Multidisciplinary Sciences
Jiye Liu, Teru Hideshima, Lijie Xing, Su Wang, Wenrong Zhou, Mehmet K. Samur, Tomasz Sewastianik, Daisuke Ogiya, Gang An, Shaobing Gao, Li Yang, Tong Ji, Giada Bianchi, Kenneth Wen, Yu-Tzu Tai, Nikhil Munshi, Paul Richardson, Ruben Carrasco, Yong Cang, Kenneth C. Anderson
Summary: Immunomodulatory drugs (IMiDs) have significantly improved patient outcomes in multiple myeloma (MM), but resistance to IMiDs is a common cause of disease relapse. Research has found that TNF receptor-associated factor 2 (TRAF2) knockdown/knockout mediates IMiD resistance in MM cells. Clinical relevance has been confirmed through RNA sequencing of MM patient samples showing ERK pathway activation at relapse on lenalidomide maintenance therapy. Combination MEK inhibitor treatment has been shown to restore IMiD sensitivity in TRAF2 KO cells in both in vitro and in vivo studies.
Article
Oncology
Yanira Ruiz-Heredia, Alejandra Ortiz-Ruiz, Mehmet K. Samur, Vanesa Garrido, Laura Rufian, Ricardo Sanchez, Pedro Aguilar-Garrido, Santiago Barrio, Miguel A. Martin, Niccolo Bolli, Yu-Tzu Tai, Raphael Szalat, Mariateresa Fulciniti, Nikhil Munshi, Joaquin Martinez-Lopez, Maria Linares, Miguel Gallardo
Summary: Analyzing mitochondrial DNA copy number (mtDNACN) in monoclonal gammopathies and multiple myeloma revealed differences related to disease progression and demonstrated the involvement of mitochondria in the pathogenesis of these diseases. The findings highlighted the importance of mtDNACN evaluation in guiding clinical decision making, especially in high-risk smoldering MM cases.
Article
Biology
Subodh Kumar, Leutz Buon, Srikanth Talluri, Marco Roncador, Chengcheng Liao, Jiangning Zhao, Jialan Shi, Chandraditya Chakraborty, Gabriel Gonzalez, Yu-Tzu Tai, Rao Prabhala, Mehmet K. Samur, Nikhil C. Munshi, Masood A. Shammas
Summary: Subodh Kumar et al. identify a gene signature correlated with genomic instability and poor survival in esophageal adenocarcinoma (EAC), using a combination of integrative genomic analysis of patient data and laboratory validation in cell line models and mice. They find that inhibitors of some of the identified proteins, including TTK, could be used to reduce genomic evolution as well as inhibit growth of EAC cells.
COMMUNICATIONS BIOLOGY
(2021)
Article
Hematology
Abdul Hamid Bazarbachi, Herve Avet-Loiseau, Raphael Szalat, Anil Aktas Samur, Zachary Hunter, Masood Shammas, Jill Corre, Mariateresa Fulciniti, Kenneth C. Anderson, Giovanni Parmigiani, Steven P. Treon, Mohamad Mohty, Nikhil C. Munshi, Mehmet Kemal Samur
Summary: Research on Immunoglobulin M (IgM) multiple myeloma (MM) identified distinguishing characteristics from other IgM-producing gammopathies, including unique translocations, chromosome deletions, and molecular signatures. IgM-MM is likely to originate from a pre-germinal center and shows potential for targeted therapeutics in clinical settings.
Article
Hematology
Debora Soncini, Claudia Martinuzzi, Pamela Becherini, Elisa Gelli, Samantha Ruberti, Katia Todoerti, Luca Mastracci, Paola Contini, Antonia Cagnetta, Antonella Laudisi, Fabio Guolo, Paola Minetto, Maurizio Miglino, Sara Aquino, Riccardo Varaldo, Daniele Reverberi, Matteo Formica, Mario Passalacqua, Alessio Nencioni, Antonino Neri, Mehmet K. Samur, Nikhil C. Munshi, Mariateresa Fulciniti, Roberto M. Lemoli, Michele Cea
Summary: Recent studies have found aberrant splicing in cancer cells and suggested it as a potential therapeutic strategy. This study evaluated the expression of spliceosome machinery components in multiple myeloma cells and found that modulating splicing can impair cell growth and survival. The findings suggest that targeting splicing could make multiple myeloma patients more vulnerable to BCL2 inhibitors.
Article
Hematology
Nicola Giesen, Nagarajan Paramasivam, Umut H. Toprak, Daniel Huebschmann, Jing Xu, Sebastian Uhrig, Mehmet Samur, Stella Baehr, Martina Froehlich, Sadaf S. Mughal, Elias K. Mai, Anna Jauch, Carsten Muller-Tidow, Benedikt Brors, Nikhil Munshi, Hartmut Goldschmidt, Niels Weinhold, Matthias Schlesner, Marc S. Raab
Summary: This study provides comprehensive genomic characterization of heavily pretreated relapsed/refractory multiple myeloma patients, revealing a complex mutational landscape and potential therapeutic targets. The findings highlight the impact of specific gene mutations on patient survival and suggest potential therapeutic implications.
Article
Multidisciplinary Sciences
Maximilian Merz, Almuth Maria Anni Merz, Jie Wang, Lei Wei, Qiang Hu, Nicholas Hutson, Cherie Rondeau, Kimberly Celotto, Ahmed Belal, Ronald Alberico, AnneMarie W. Block, Hemn Mohammadpour, Paul K. Wallace, Joseph Tario, Jesse Luce, Sean T. Glenn, Prashant Singh, Megan M. Herr, Theresa Hahn, Mehmet Samur, Nikhil Munshi, Song Liu, Philip L. McCarthy, Jens Hillengass
Summary: This study characterizes osteolytic lesions (OL) in multiple myeloma patients using single-cell RNA sequencing (scRNA-seq), revealing specifically regulated genes in OL compared to random bone marrow samples, as well as their response to induction therapy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ram Ajore, Abhishek Niroula, Maroulio Pertesi, Caterina Cafaro, Malte Thodberg, Molly Went, Erik L. Bao, Laura Duran-Lozano, Aitzkoa Lopez de Lapuente Portilla, Thorunn Olafsdottir, Nerea Ugidos-Damboriena, Olafur Magnusson, Mehmet Samur, Caleb A. Lareau, Gisli H. Halldorsson, Gudmar Thorleifsson, Gudmundur L. Norddahl, Kristbjorg Gunnarsdottir, Asta Foersti, Hartmut Goldschmidt, Kari Hemminki, Frits van Rhee, Scott Kimber, Adam S. Sperling, Martin Kaiser, Kenneth Anderson, Ingileif Jonsdottir, Nikhil Munshi, Thorunn Rafnar, Anders Waage, Niels Weinhold, Unnur Thorsteinsdottir, Vijay G. Sankaran, Kari Stefansson, Richard Houlston, Bjorn Nilsson
Summary: This integrative study investigates over a thousand variants associated with multiple myeloma, identifying potential causal variants at six risk loci and highlighting the role of gene-regulatory changes in plasma cells and B-cells in mediating disease susceptibility.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Romain Lannes, Mehmet Samur, Aurore Perrot, Celine Mazzotti, Marion Divoux, Titouan Cazaubiel, Xavier Leleu, Anais Schavgoulidze, Marie-Lorraine Chretien, Salomon Manier, Didier Adiko, Frederique Orsini-Piocelle, Francois Lifermann, Sabine Brechignac, Lauris Gastaud, Didier Bouscary, Margaret Macro, Alice Cleynen, Mohamad Mohty, Nikhil Munshi, Jill Corre, Herve Avet-Loiseau
Summary: Using single-cell genomics, it was found that high-risk events in multiple myeloma (MM) patients are often missed at diagnosis and only selected at relapse. This suggests the need for more aggressive treatment at diagnosis to prevent these aggressive cells from becoming dominant clones.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Keiji Kurata, Anna-James Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
Summary: Multiple myeloma (MM) is a plasma cell malignancy associated with aberrant immunoglobulin production and proteotoxic stress. In this study, we identified glutamyl-prolyl-tRNA synthetase (GluProRS) as a potential therapeutic target. By developing a novel inhibitor called NCP26, we demonstrated its significant anti-tumour activity in various in vitro and in vivo systems, overcoming metabolic adaptation observed with other inhibitors. Our findings suggest a complex pro-apoptotic response beyond the integrated stress response, involving downregulated proline-rich motif-containing proteins as downstream effectors and establishing a novel determinant in MM pathobiology.
BLOOD CANCER JOURNAL
(2023)
Correction
Oncology
Keiji Kurata, Anna James-Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
BLOOD CANCER JOURNAL
(2023)
Article
Multidisciplinary Sciences
Ram Ajore, Abhishek Niroula, Maroulio Pertesi, Caterina Cafaro, Malte Thodberg, Molly Went, Erik L. Bao, Laura Duran-Lozano, Aitzkoa Lopez de Lapuente Portilla, Thorunn Olafsdottir, Nerea Ugidos-Damboriena, Olafur Magnusson, Mehmet Samur, Caleb A. Lareau, Gisli H. Halldorsson, Gudmar Thorleifsson, Gudmundur L. Norddahl, Kristbjorg Gunnarsdottir, Asta Forsti, Hartmut Goldschmidt, Kari Hemminki, Frits van Rhee, Scott Kimber, Adam S. Sperling, Martin Kaiser, Kenneth Anderson, Ingileif Jonsdottir, Nikhil Munshi, Thorunn Rafnar, Anders Waage, Niels Weinhold, Unnur Thorsteinsdottir, Vijay G. Sankaran, Kari Stefansson, Richard Houlston, Bjorn Nilsson
Summary: In this study, non-coding variants associated with multiple myeloma (MM) were investigated using a combination of methods. The results showed that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identified potential causal variants at six risk loci. Three of these variants were found to have causal activity at specific genomic positions in an endogenous chromosomal context in vivo. This study provides a systematic functional analysis of risk loci for a hematologic malignancy.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Annamaria Gulla, Eugenio Morelli, Mehmet K. Samur, Cirino Botta, Teru Hideshima, Giada Bianchi, Mariateresa Fulciniti, Stefano Malvestiti, Rao H. Prabhala, Srikanth Talluri, Kenneth Wen, Yu-Tzu Tai, Paul G. Richardson, Dharminder Chauhan, Tomasz Sewastianik, Ruben D. Carrasco, Nikhil C. Munshi, Kenneth C. Anderson
Summary: The study demonstrates that bortezomib induces immunogenic cell death in multiple myeloma cells by activating the cGAS/STING pathway and producing type I IFNs, leading to improved patient outcomes. The findings suggest that combining STING agonists with bortezomib could enhance tumor-specific immunity and benefit patients with multiple myeloma.
BLOOD CANCER DISCOVERY
(2021)
Article
Oncology
Hiroto Ohguchi, Paul M. C. Park, Tingjian Wang, Berkley E. Gryder, Daisuke Ogiya, Keiji Kurata, Xiaofeng Zhang, Deyao Li, Chengkui Pei, Takeshi Masuda, Catrine Johansson, Virangika K. Wimalasena, Yong Kim, Shinjiro Hino, Shingo Usuki, Yawara Kawano, Mehmet K. Samur, Yu-Tzu Tai, Nikhil C. Munshi, Masao Matsuoka, Sumio Ohtsuki, Mitsuyoshi Nakao, Takashi Minami, Shannon Lauberth, Javed Khan, Udo Oppermann, Adam D. Durbin, Kenneth C. Anderson, Teru Hideshima, Jun Qi
Summary: The study revealed that KDM5A can interact with the P-TEFb complex and cooperate with MYC to control MYC-targeted genes in multiple myeloma cells. They developed a KDM5 inhibitor, JQKD82, which paradoxically increases H3K4me3 but inhibits downstream MYC-driven transcriptional output in vitro and in vivo.
BLOOD CANCER DISCOVERY
(2021)