Article
Microbiology
David W. Morgens, Divya Nandakumar, Allison L. Didychuk, Kevin J. Yang, Britt A. Glaunsinger
Summary: This study demonstrates the use of CRISPR/Cas9 to rapidly create and screen thousands of mutant viruses in Kaposi's sarcoma-associated herpesvirus (KSHV). By analyzing the expression of viral genes in these mutant viruses, a novel required gene was identified and its specific function was characterized using targeted deep viral sequencing.
Article
Medicine, Research & Experimental
Samir H. Barghout, Ahmed Aman, Kazem Nouri, Zachary Blatman, Karen Arevalo, Geethu E. Thomas, Neil MacLean, Rose Hurren, Troy Ketela, Mehakpreet Saini, Moustafa Abohawya, Taira Kiyota, Rima Al-Awar, Aaron D. Schimmer
Summary: The study revealed that the BEND3 gene plays a crucial role in the sensitivity of cancer drug TAK-243, with its knockout reducing the drug's impact on cancer cells. Knocking out BEND3 also affects the expression levels of BCRP, thereby regulating the intracellular levels of the drug TAK-243.
Article
Chemistry, Medicinal
Laia Josa-Cullere, Katrina S. Madden, Thomas J. Cogswell, Thomas R. Jackson, Tom S. Carter, Douzi Zhang, Graham Trevitt, Stephen G. Davies, Paresh Vyas, Graham M. Wynne, Thomas A. Milne, Angela J. Russell
Summary: A novel compound, OXS007417, identified through a phenotypic high-throughput screen, shows promise in decreasing tumor volume in acute myeloid leukemia.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Chunhua Wan, Sylvia Mahara, Claire Sun, Anh Doan, Hui Kheng Chua, Dakang Xu, Jia Bian, Yue Li, Danxi Zhu, Dhanya Sooraj, Tomasz Cierpicki, Jolanta Grembecka, Ron Firestein
Summary: The aberrant activation of the Wnt/beta-catenin pathway is a key driver of colorectal cancer growth, and in this study, KMT2A is identified as a promising target for CRC therapy due to its unique epigenetic regulation of beta-catenin transcriptional output.
Article
Biochemistry & Molecular Biology
Annika Kratzel, Jenna N. Kelly, Philip V'kovski, Jasmine Portmann, Yannick Brueggemann, Daniel Todt, Nadine Ebert, Neeta Shrestha, Philippe Plattet, Claudia A. Staab-Weijnitz, Albrecht von Brunn, Eike Steinmann, Ronald Dijkman, Gert Zimmer, Stephanie Pfaender, Volker Thiel
Summary: Over the past 20 years, three highly pathogenic human coronaviruses have emerged, highlighting the serious threat that coronaviruses pose to human health. Research has identified several autophagy-related genes as common host factors required for the replication of coronaviruses, suggesting potential targets for therapeutic intervention using clinically approved drugs.
Article
Hematology
Vaidehi Krishnan, Florian Schmidt, Zahid Nawaz, Prasanna Nori Venkatesh, Kian Leong Lee, Xi Ren, Zhu En Chan, Mengge Yu, Meera Makheja, Nirmala Arul Rayan, Michelle Gek Liang Lim, Alice Man Sze Cheung, Sudipto Bari, Wee Joo Chng, Hein Than, John Ouyang, Owen Rackham, Tuan Zea Tan, William Ying Khee Hwang, Charles Chuan, Shyam Prabhakar, S. Tiong Ong
Summary: Using single-cell RNA sequencing, we identified 8 significant features in the bone marrow of chronic myeloid leukemia patients that correlated with sensitivity or resistance to imatinib treatment. By employing machine learning, we accurately predicted imatinib response with over 80% accuracy, including no false positives for predicting blast crisis transformation. Patients with major molecular response exhibited a signature erythroid-specifying regulon, while those who progressed to transformation showed an inflammatory regulon.
Article
Cell & Tissue Engineering
Tiansu Wang, Allison R. Pine, Andriana G. Kotini, Han Yuan, Lee Zamparo, Daniel T. Starczynowski, Christina Leslie, Eirini P. Papapetrou
Summary: Through the combination of induced pluripotent stem cell (iPSC) and CRISPR-Cas9 technologies, a model of clonal evolution of acute myeloid leukemia (AML) was successfully developed. This model captured distinct premalignant stages and genetic features of primary human MDS and AML, ultimately identifying dysregulation of inflammatory signaling as an early and persistent event in leukemogenesis and a potential therapeutic target.
Article
Oncology
Borhan R. Saeed, Linda Manta, Simon Raffel, Paul Theodor Pyl, Eike C. Buss, Wenwen Wang, Volker Eckstein, Anna Jauch, Andreas Trumpp, Wolfgang Huber, Anthony D. Ho, Christoph Lutz
Summary: Through whole-exome sequencing of leukemia and nonleukemia compartments from AML patients, mutations were identified in both compartments with some novel mutations found. The presence of leukemia-specific mutations in nonleukemia compartments suggests a possible source of leukemogenesis and may contribute to disease relapse.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Cell Biology
Fang Cao, Yunpeng Jiang, Lin Chang, Hongzhen Du, De Chang, Chunxiao Pan, Xiaozheng Huang, Donglin Yu, Mi Zhang, Yongna Fan, Xiaocui Bian, Kailong Li
Summary: Pancreatic cancer is characterized by early metastasis and limited response to current therapies. Through a genetic screening platform, YWHAZ has been identified as a key regulator of pancreatic cancer metastasis. Overexpression of YWHAZ promotes cell migration and invasion, and is associated with poor prognosis in pancreatic cancer patients.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Wei-Yu Lin, Sarah E. Fordham, Eric Hungate, Nicola J. Sunter, Claire Elstob, Yaobo Xu, Catherine Park, Anne Quante, Konstantin Strauch, Christian Gieger, Andrew Skol, Thahira Rahman, Lara Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I. Clay-Gilmour, Gail L. Jones, Helen J. Marr, Graham H. Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K. Hills, Alan K. Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J. Allsup, Richard S. Houlston, Jean Norden, Anne M. Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhauser, Christoph Rollig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenfuhr, Heather J. Cordell, Rebecca Darlay, Mette K. Andersen, Maria C. Fontana, Giovanni Martinelli, Giovani Marconi, Miguel A. Sanz, Jose Cervera, Ines Gomez-Segui, Thomas Cluzeau, Chimene Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Herve Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E. Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsan, Csaba Bodor, Friedrich Stolzel, Kenan Onel, James M. Allan
Summary: The study conducted a genome-wide association analysis on European patients with AML, identifying genetic loci associated with the risk of developing the disease. The results shed light on potential functional genes involved in histone methylation and immune function in AML etiology.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Wen Hao Neo, Yiran Meng, Alba Rodriguez-Meira, Muhammad Z. H. Fadlullah, Christopher A. G. Booth, Emanuele Azzoni, Supat Thongjuea, Marella F. T. R. de Bruijn, Sten Eirik W. Jacobsen, Adam J. Mead, Georges Lacaud
Summary: The study reveals the crucial role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE. Loss of EZH2 activity in HE leads to the generation of non-functional EMPs due to a lack of Wnt signaling downregulation, while the generation of primitive erythroid cells is not affected. EZH2 is essential for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but becomes dispensable later on.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Bin E. Li, Grace Y. Li, Wenqing Cai, Qian Zhu, Davide Seruggia, Yuko Fujiwara, Christopher R. Vakoc, Stuart H. Orkin
Summary: Through CRISPR/Cas9 screening and in vivo phenotypic readouts, we revealed a novel role for the Pbrm1 gene in leukemia progression and demonstrated that transcriptional control of interferon signaling influences the interaction between leukemia cells and the immune system.
Article
Biochemistry & Molecular Biology
Jacob Jalil Hassan, Anna Lieske, Nicole Doerpmund, Denise Klatt, Dirk Hoffmann, Marc-Jens Kleppa, Olga S. Kustikova, Maike Stahlhut, Adrian Schwarzer, Axel Schambach, Tobias Maetzig
Summary: Through gene expression analysis and gene set enrichment analyses, 15 candidates for functional validation were compiled. H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A) was identified using a novel lentiviral multiplexing approach. Pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells and showed potential therapeutic effects in AML with MLL rearrangement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Casey Ah-Cann, Verena C. Wimmer, Clare E. Weeden, Claire Marceaux, Charity W. Law, Laura Galvis, Caitlin E. Filby, Joy Liu, Kelsey Breslin, Tracy Willson, Matthew E. Ritchie, Marnie E. Blewitt, Marie-Liesse Asselin-Labat
Summary: The development of a branching tree in the embryonic lung is crucial for a fully mature functional lung at birth, with Sox9(+) cells playing a key role in this process. This study identified aurora kinase b (Aurkb) as an essential regulator of Sox9(+) cells, with its loss leading to insufficient branch development. The research demonstrates the potential of genetic screens in identifying regulators of lung development.
Article
Oncology
Xiaoxia Hu, Bianhong Wang, Qi Chen, Aijie Huang, Weijia Fu, Lixia Liu, Ying Zhang, Gusheng Tang, Hui Cheng, Xiong Ni, Lei Gao, Jie Chen, Li Chen, Weiping Zhang, Jianmin Yang, Shanbo Cao, Li Yu, Jianmin Wang
Summary: The study established a prediction model to identify intermediate risk AML patients with inferior survival, based on characteristics such as white blood cell count, mutated DNMT3A, and genes involved in signaling pathways. The model accurately predicted overall survival and relapse-free survival and was validated with two independent cohorts. Allogeneic hematopoietic stem cell transplantation significantly reduced the relapse risk for intermediate high-risk patients.
Article
Hematology
Maximilian Stahl, Andriy Derkach, Noushin Farnoud, Jan Philipp Bewersdorf, Troy Robinson, Christopher Famulare, Christina Cho, Sean Devlin, Kamal Menghrajani, Minal A. Patel, Sheng F. Cai, Linde A. Miles, Robert L. Bowman, Mark B. Geyer, Andrew Dunbar, Zachary D. Epstein-Peterson, Erin McGovern, Jessica Schulman, Jacob L. Glass, Justin Taylor, Aaron D. Viny, Eytan M. Stein, Bartlomiej Getta, Maria E. Arcila, Qi Gao, Juliet Barker, Brian C. Shaffer, Esperanza B. Papadopoulos, Boglarka Gyurkocza, Miguel-Angel Perales, Omar Abdel-Wahab, Ross L. Levine, Sergio A. Giralt, Yanming Zhang, Wenbin Xiao, Nidhi Pai, Elli Papaemmanuil, Martin S. Tallman, Mikhail Roshal, Aaron D. Goldberg
Summary: Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). This study aims to identify pre-treatment molecular predictors of immunophenotypic MRD clearance in AML patients. The results showed that induction chemotherapy led to different MRD responses, with 35% achieving MRD- remission, 27% achieving MRD+ remission, and 38% having persistent disease. Subsequent therapy resulted in MRD conversion in 34% of MRD+ patients and 26% of patients with persistent disease. Specific gene mutations and karyotypic abnormalities were found to be associated with high or low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Furthermore, the study demonstrated that achieving MRD- prior to allogeneic stem cell transplant (allo-SCT) was associated with favorable outcomes. Therefore, the inclusion of patients with specific baseline mutational patterns and high clone numbers in clinical trials should be considered.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Matteo Gentili, Bingxu Liu, Malvina Papanastasiou, Deborah Dele-Oni, Marc A. Schwartz, Rebecca J. Carlson, Aziz M. Al'Khafaji, Karsten Krug, Adam Brown, John G. Doench, Steven A. Carr, Nir Hacohen
Summary: In this study, genes regulating STING trafficking were systematically characterized, and their impact on STING-mediated responses was examined. The study revealed that the ESCRT complex promotes STING degradation and terminates STING signaling. Furthermore, a UBAP1 mutation was found to increase steady-state STING-dependent responses. Overall, this study uncovers the role of the ESCRT complex in regulating STING signaling.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Andrew J. Dunbar, Dongjoo Kim, Min Lu, Mirko Farina, Robert L. Bowman, Julie L. Yang, Young Park, Abdul Karzai, Wenbin Xiao, Zach Zaroogian, Kavi O'Connor, Shoron Mowla, Francesca Gobbo, Paola Verachi, Fabrizio Martelli, Giuseppe Sarli, Lijuan Xia, Nada Elmansy, Maria Kleppe, Zhuo Chen, Yang Xiao, Erin McGovern, Jenna Snyder, Aishwarya Krishnan, Corrine Hill, Keith Cordner, Anouar Zouak, Mohamed E. Salama, Jayden Yohai, Eric Tucker, Jonathan Chen, Jing Zhou, Timothy McConnell, Anna R. Migliaccio, Richard Koche, Raajit Rampal, Rong Fan, Ross L. Levine, Ronald Hoffman
Summary: Inflammatory signaling is crucial in the development of myelofibrosis (MF), a type of cancer. Recent studies have identified the involvement of JAK/STAT and NF-kappa B signaling in MF progression. This study further explores the role of CXCL8/CXCR2 signaling in MF pathogenesis, and highlights its potential as a therapeutic target.
Article
Oncology
James M. Foran, Zhuoxin Sun, Catherine Lai, Hugo F. Fernandez, Larry D. Cripe, Rhett P. Ketterling, Janis Racevskis, Selina M. Luger, Elisabeth Paietta, Hillard M. Lazarus, Yanming Zhang, John M. Bennett, Ross L. Levine, Jacob M. Rowe, Mark R. Litzow, Martin S. Tallman
Summary: This study examined the association of obesity with AML and its impact on clinical outcomes. The results showed that obesity was associated with certain clinical and genetic features of AML, but did not affect patient survival.
Article
Oncology
Vu H. Duong, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William Blum, Martha L. Arellano, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Prapti A. Patel, Matthew C. Foster, Robert L. Redner, Zeina Al-Mansour, Christopher R. Cogle, Ronan T. Swords, Robert H. Collins, Jo-Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Ashley O. Yocum, Sonja Marcus, Timothy Chen, Franchesca Druggan, Mona Stefanos, Theophilus J. Gana, Abigail B. Shoben, Brian J. Druker, Amy Burd, John C. Byrd, Ross L. Levine, Michael M. Boyiadzis
Summary: This study evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in patients with acute myeloid leukemia (AML) who have poor prognosis. The combination showed some activity and acceptable tolerance, but the complete remission rates were low and overall survival was short.
Article
Endocrinology & Metabolism
Laura Boucai, Ryan N. Ptashkin, Ross L. Levine, James A. Fagin
Summary: In this prospective cohort study, the effects of therapeutic radioactive iodine (RAI) on clonal hematopoiesis (CH) were examined. The results showed no increase in CH in patients treated with RAI over a 2-year follow-up period. It was also found that the presence of CH was associated with worse structural progression in both BRAFV600E-mutant and wild-type thyroid cancers.
CLINICAL ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mehdi Ghram, Gavin Morris, Biljana Culjkovic-Kraljacic, Jean-Clement Mars, Patrick Gendron, Lucy Skrabanek, Maria Victoria Revuelta, Leandro Cerchietti, Monica L. Guzman, Katherine L. B. Borden
Summary: Aberrant splicing, a known contributor to malignancies, is usually attributed to splice-factor mutation. This study, however, discovered a mutation-independent mechanism for extensively reprogramming alternative splicing (AS) in acute myeloid leukemia (AML). The dysregulated expression of eukaryotic translation initiation factor eIF4E was found to increase selective splice-factor production, thereby affecting multiple spliceosome complexes and generating a splicing landscape that supported altered splice-site selection for hundreds of transcripts in AML patients with high-eIF4E expression.
Article
Multidisciplinary Sciences
Florian Perner, Eytan M. M. Stein, Daniela V. V. Wenge, Sukrit Singh, Jeonghyeon Kim, Athina Apazidis, Homa Rahnamoun, Disha Anand, Christian Marinaccio, Charlie Hatton, Yanhe Wen, Richard M. M. Stone, David Schaller, Shoron Mowla, Wenbin Xiao, Holly A. A. Gamlen, Aaron J. J. Stonestrom, Sonali Persaud, Elizabeth Ener, Jevon A. A. Cutler, John G. G. Doench, Gerard M. M. McGeehan, Andrea Volkamer, John D. D. Chodera, Radoslaw P. Nowak, Eric S. S. Fischer, Ross L. L. Levine, Scott A. A. Armstrong, Sheng F. F. Cai
Summary: Chromatin-binding proteins are important regulators of cell state in haematopoiesis. Clinical trials have shown that the menin inhibitor revumenib can treat leukaemia with KMT2Ar or NPM1 mutations. However, acquired resistance to menin inhibition may be caused by somatic mutations in the MEN1 gene.
Article
Medicine, Research & Experimental
Tianxia Li, Osamu Kikuchi, Jin Zhou, Yichen Wang, Babita Pokharel, Klavdija Bastl, Prafulla Gokhale, Aine Knott, Yanxi Zhang, John G. Doench, Zandra V. Ho, Daniel V. T. Catenacci, Adam J. Bass
Summary: Gastroesophageal adenocarcinomas (GEAs) frequently exhibit amplification of KRAS gene, resulting in overexpression of WT KRAS protein. This study investigates potential targets to enhance the efficacy of SHP2 inhibition in KRAS-amplified GEA, including those within the MAPK pathway and upstream RTKs. In vitro and in vivo experiments demonstrate that pan-ERBB kinase inhibition has potent cytotoxicity. Additionally, the combination of CDK4/6 inhibition with SHP2 inhibition shows greater efficacy in KRAS-amplified GEA compared to KRAS-mutant tumors. These findings suggest potential therapeutic combinations for clinical study in KRAS-amplified GEAs.
Article
Multidisciplinary Sciences
Charles Zou, Hojong Yoon, Paul M. C. Park, J. J. Patten, Jesse Pellman, Jeannie Carreiro, Jonathan M. Tasi, Yen-Der Li, Shourya S. Roy Burman, Katherine A. Donovan, Jessica Gasser, Adam S. Sperling, Radoslaw P. Nowak, Eric S. Fischer, Robert A. Davey, Benjamin L. Ebert, Mikolaj Slabicki
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes multiple human proteins during infection and replication. Researchers have discovered that the human E3 ubiquitin ligase RNF185 plays a role in regulating the stability of the SARS-CoV-2 envelope protein. This interaction occurs at the endoplasmic reticulum (ER) and depletion of RNF185 leads to an increase in SARS-CoV-2 viral titer. This finding suggests that modulating this interaction could be a potential strategy for developing antiviral therapies.
Article
Oncology
Ricardo de Matos Simoes, Ryosuke Shirasaki, Sondra L. Downey-Kopyscinski, Geoffrey M. Matthews, Benjamin G. Barwick, Vikas A. Gupta, Daphne Dupere-Richer, Shizuka Yamano, Yiguo Hu, Michal Sheffer, Eugen Dhimolea, Olga Dashevsky, Sara Gandolfi, Kazuya Ishiguro, Robin M. Meyers, Jordan G. Bryan, Neekesh V. Dharia, Paul J. Hengeveld, Johanna B. Bruggenthies, Huihui Tang, Andrew J. Aguirre, Quinlan L. Sievers, Benjamin L. Ebert, Brian J. Glassner, Christopher J. Ott, James E. Bradner, Nicholas P. Kwiatkowski, Daniel Auclair, Joan Levy, Jonathan J. Keats, Richard W. J. Groen, Nathanael S. Gray, Aedin C. Culhane, James M. McFarland, Joshua M. Dempster, Jonathan D. Licht, Lawrence H. Boise, William C. Hahn, Francisca Vazquez, Aviad Tsherniak, Constantine S. Mitsiades
Summary: Clinical progress in multiple myeloma has been limited due to the lack of therapies targeting specific oncogenic mutations. However, a study using CRISPR technology identified 116 genes that significantly affect the fitness of MM cells compared to other malignancies. These genes encode various factors critical for MM cell biology and provide new therapeutic targets not easily identifiable by standard genomic analysis.
Article
Biochemistry & Molecular Biology
Pablo Sanchez Vela, Jennifer J. J. Trowbridge, Ross L. L. Levine
Summary: New data reveals the surprising association between clonal hematopoiesis and protection from Alzheimer's disease, highlighting the need for future studies to unravel the complex mechanisms underlying the role of clonal hematopoiesis in tissue-disease contexts and aging-associated diseases.
Article
Medicine, Research & Experimental
Santhosh Kumar Pasupuleti, Baskar Ramdas, Sarah S. Burns, Lakshmi Reddy Palam, Rahul Kanumuri, Ramesh Kumar, Taruni Reddy Pandhiri, Utpal P. Dave, Nanda Kumar Yellapu, Xinyu Zhou, Chi Zhang, George E. Sandusky, Zhi Yu, Michael C. Honigberg, Alexander G. Bick, Gabriel K. Griffin, Abhishek Niroula, Benjamin L. Ebert, Sophie Paczesny, Pradeep Natarajan, Reuben Kapur
Summary: Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis of indeterminate potential (CHIP) is associated with obesity and could potentially be treated using targeted drugs.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Hematology
Sofia von Palffy, Hanna Thorsson, Pablo Pena-Martinez, Noelia Puente-Moncada, Carl Sanden, Anna M. Blom, Rasmus Henningsson, Gunnar Juliusson, Ben King, Niklas Landberg, Vladimir Lazarevic, Christina Orsmark-Pietras, Marianne Rissler, Vendela Rissler, Helena Agerstam, Marcus Jaras, Henrik Lilljebjorn, Thoas Fioretos
Summary: Mutations in the NPM1 gene are common in acute myeloid leukemia (AML), but relapse is still a significant concern. In this study, we identified the complement receptor C3AR as specifically expressed in NPM1-mutated AML cells, making it a potential target for antibody-based therapies. We also found that C3AR, in combination with GPR56, distinguishes leukemic stem cells from normal hematopoietic stem cells, and stimulation of C3AR-expressing cells leads to increased survival of AML cells. Furthermore, antibodies directed against C3AR effectively induce natural killer cell-mediated killing of primary AML cells, highlighting its potential as a therapeutic target in NPM1-mutated AML.
Article
Medicine, Research & Experimental
Zhi Yu, Trevor P. Fidler, Yunfeng Ruan, Caitlyn Vlasschaert, Tetsushi Nakao, Md Mesbah Uddin, Taralynn Mack, Abhishek Niroula, J. Brett Heimlich, Seyedeh M. Zekavat, Christopher J. Gibson, Gabriel K. Griffin, Yuxuan Wang, Gina M. Peloso, Nancy Heard-Costa, Daniel Levy, Ramachandran S. Vasan, Francois Aguet, Kristin G. Ardlie, Kent D. Taylor, Stephen S. Rich, Jerome I. Rotter, Peter Libby, Siddhartha Jaiswal, Benjamin L. Ebert, Alexander G. Bick, Alan R. Tall, Pradeep Natarajan
Summary: This study investigated the role of inflammatory gene modifiers in CHIP-associated CVD risk and found IL1RAP and AIM2 as key molecules in modulating this risk. The study also supported gene-specific strategies for addressing CHIP-associated CVD risk.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
