Article
Multidisciplinary Sciences
Kristina Ames, Imit Kaur, Yang Shi, Meng M. Tong, Taneisha Sinclair, Shayda Hemmati, Shira G. Glushakow-Smith, Ellen Tein, Lindsay Gurska, Ulrich Steidl, Robert Dubin, Jidong Shan, Cristina Montagna, Kith Pradhan, Amit Verma, Kira Gritsman
Summary: Myelodysplastic syndrome (MDS) is a clonal malignancy in hematopoietic stem cells (HSCs) with poorly understood mechanisms. A study shows that down-regulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway can lead to MDS initiation in HSCs. The study also demonstrates that PI3K plays a protective role in maintaining autophagic flux in HSCs to prevent MDS.
Article
Oncology
Honglan Qu, Gao-wa Hasen, Yanyan Hou, Mengwei Ren, Jun Li, Baoshong Jing, YanDan Du
Summary: TRIM37 is upregulated in T-cell acute lymphoblastic leukemia (T-ALL), and it promotes the proliferation and reduces the sensitivity of T-ALL cells to bortezomib treatment by enhancing PTEN degradation and activating PI3K/AKT signaling pathway. These findings suggest that TRIM37 could be a potential therapeutic target for T-ALL.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Patrick Ehm, Astrid Grottke, Bettina Bettin, Manfred Juecker
Summary: Acute lymphoblastic leukemia, the leading cause of cancer-related death in children, has a poor prognosis. However, a new therapeutic approach targeting the PI3K/AKT/mTOR signaling pathway shows promising results in inhibiting cancer cell growth and overcoming cell resistance.
CELLULAR SIGNALLING
(2022)
Article
Cell Biology
Carol Dangelmaier, Satya P. Kunapuli
Summary: The study revealed that PI-3 Kinase plays a crucial role in platelet activation by regulating RASA3 and leading to Akt phosphorylation. LY294002 can inhibit Akt phosphorylation induced by certain stimuli at low concentrations, while higher concentrations may inhibit other pathways regulating Akt phosphorylation. Additionally, Protease-activated receptor 4 (PAR4) may cause Akt phosphorylation through distinct pathways compared to Protease-activated receptor 1 (PAR1).
Article
Multidisciplinary Sciences
James R. W. Conway, Sean C. Warren, Young-Kyung Lee, Andrew T. McCulloch, Astrid Magenau, Victoria Lee, Xanthe L. Metcalf, Janett Stoehr, Katharina Haigh, Lea Abdulkhalek, Cristian S. Guaman, Daniel A. Reed, Kendelle J. Murphy, Brooke A. Pereira, Pauline Melenec, Cecilia Chambers, Sharissa L. Latham, Helen Lenthall, Elissa K. Deenick, Yuanqing Ma, Tri Phan, Elgene Lim, Anthony M. Joshua, Stacey Walters, Shane T. Grey, Yan-Chuan Shi, Lei Zhang, Herbert Herzog, David R. Croucher, Andy Philp, Colinda L. G. J. Scheele, David Herrmann, Owen J. Sansom, Jennifer P. Morton, Antonella Papa, Jody J. Haigh, Max Nobis, Paul Timpson
Summary: Aberrant AKT activation is implicated in various diseases, and therefore targeting AKT has become a significant approach for disease treatment. In this study, we developed an Akt-FRET biosensor mouse that enables the monitoring of AKT activity in live tissues. We demonstrated the sensitivity of this biosensor mouse in different cancer models and showed its suitability for evaluating drug response. Additionally, we observed real-time dynamics of AKT activation in diverse tissues, indicating the broad preclinical applications of this biosensor mouse for studying AKT dynamics in vivo.
Editorial Material
Hematology
Josep-Maria Ribera
Summary: In this study, the prognostic significance of central nervous system (CNS) leukemic involvement in children and young adults diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) was assessed. Patients with CNS-1 or CNS-2 status at diagnosis had similar event-free survival (EFS) and overall survival (OS), which were significantly better than those of patients with CNS-3 status.
Review
Oncology
Tina Kuenz, Alexander W. Hauswirth, Gabriele Hetzenauer, Jakob Rudzki, David Nachbaur, Normann Steiner
Summary: Improved understanding of acute lymphoblastic leukemia has led to new treatment strategies, including measurable residual disease assessment and allogeneic stem cell transplantation. Novel therapeutic opportunities, such as tyrosine-kinase inhibitors and CAR-T cells, aim to improve clinical outcomes. Despite advancements, acute lymphoblastic leukemia remains a challenging and life-threatening disease.
Article
Cell Biology
Manuel Olazabal-Moran, Miriam Sanchez-Ortega, Laura Martinez-Munoz, Carmen Hernandez, Manuel S. Rodriguez, Mario Mellado, Ana C. Carrera
Summary: PI3-kinase and PTEN regulate the PIP3/AKT signaling pathway through the ubiquitin ligase cCBL, influencing cell survival, division, and migration. These findings reveal a novel mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL may be a potential target for modulating PTEN activity in cancer.
Article
Multidisciplinary Sciences
Chenfeng Liu, Lei Ma, Yuxuan Wang, Jiayi Zhao, Pengda Chen, Xian Chen, Yingxin Wang, Yanyan Hu, Yun Liu, Xian Jia, Zhanghua Yang, Xingzhi Yin, Jianfeng Wu, Suqin Wu, Haiping Zheng, Xiaohong Ma, Xiufeng Sun, Ying He, Lianghua Lin, Yubing Fu, Kunyu Liao, Xiaojuan Zhou, Shan Jiang, Guofeng Fu, Jian Tang, Wei Han, Xiao Lei Chen, Wenzhu Fan, Yazhen Hong, Jiahuai Han, Xiangyang Huang, Bo-An Li, Nengming Xiao, Changchun Xiao, Guo Fu, Wen-Hsien Liu
Summary: The study revealed the crucial role of GSK3 in thymocyte egress and identified a previously unknown signaling function of beta-catenin in the cytoplasm.
Review
Pharmacology & Pharmacy
Ayda Baghery Saghchy Khorasani, Atieh Pourbagheri-Sigaroodi, Ali Pirsalehi, Ava Safaroghli-azar, Mohammad Reza Zali, Davood Bashash
Summary: Genetic and epigenetic alterations have long been the focus of cancer pathogenesis research, with dysregulated genes and protein products potentially affecting cancer cell growth through signaling cascades regulating cell survival and metabolism. The activation of the phosphatidylinositol-3-kinase (PI3K) axis in about one-third of human cancers, including gastric cancer, plays a significant role in the development of malignancies. This indicates the potential importance of targeting this axis in therapeutic strategies for such cancers.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hiroshi Senoo, Daisuke Murata, May Wai, Kenta Arai, Wakiko Iwata, Hiromi Sesaki, Miho Iijima
Summary: AKT, a serine/threonine kinase, plays a crucial role in metabolism, cell growth, and cytoskeletal dynamics, and is activated by PDK1 and mTORC2. Research has uncovered that insulin activates mTORC2 towards AKT by forming a supercomplex KARATE with KRAS4B and RHOA GTPases, revealing a fundamental mechanism in insulin-regulated glucose homeostasis.
Article
Biology
In-Gyu Kim, Jei-Ha Lee, Seo-Yeon Kim, Chang-Kyu Heo, Rae-Kwon Kim, Eun-Wie Cho
Summary: It was found that TSPYL5 regulates cancer stem cell-associated genes in non-small cell lung cancer cells and may serve as a target for therapy-resistant cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Katerina Hlozkova, Ivana Hermanova, Lucie Safrhansova, Natividad Alquezar-Artieda, Daniela Kuzilkova, Adela Vavrova, Kristyna Sperkova, Marketa Zaliova, Jan Stary, Jan Trka, Julia Starkova
Summary: In this study, the relationship among PTEN deletion, ASNase sensitivity, and glucose metabolism in T-ALL cells was investigated. It was found that aberrant PTEN/PI3K/Akt signaling may contribute to the therapeutic challenge of T-ALL. Furthermore, pharmacological inhibition of Akt can enhance the sensitivity of T-ALL cells to ASNase, providing a promising therapeutic option for T-ALL patients.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Liujie Zheng, Yunfeng Yao, Dasheng Luo, Zhiwei Han, Xin Zhang, Nanyu Pang, Mingyang Ding, Houlong Ye, Keyan Zhu, Wenkai Yi
Summary: Our study aimed to investigate the mechanism by which iron influences chondrocyte phenotype in the pathogenesis of haemophilic cartilage destruction. We found that iron affected chondrocyte phenotype by inhibiting the PTEN/PI3K/AKT/FOXO1 pathway.
Article
Oncology
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Hematology
Ashley Pandolfi, Robert F. Stanley, Yiting Yu, Boris Bartholdy, Gopichand Pendurti, Kira Gritsman, Jacqueline Boultwood, Jonathan Chernoff, Amit Verma, Ulrich Steidl
Letter
Oncology
S. Goel, J. Hall, K. Pradhan, C. Hirsch, B. Przychodzen, A. Shastri, I. Mantzaris, M. Janakiram, R. Battini, N. Kornblum, O. Derman, K. Gritsman, J. Al-Hafidh, Y. Wang, B. Halmos, U. Steidl, J. P. Maciejewski, I. Braunschweig, A. Verma
Article
Immunology
Murali K. Akula, Man Shi, Zhaozhao Jiang, Celia E. Foster, David Miao, Annie S. Li, Xiaoman Zhang, Ruth M. Gavin, Sorcha D. Forde, Gail Germain, Susan Carpenter, Charles V. Rosadini, Kira Gritsman, Jae Jin Chae, Randolph Hampton, Neal Silverman, Ellen M. Gravallese, Jonathan C. Kagan, Katherine A. Fitzgerald, Daniel L. Kastner, Douglas T. Golenbock, Martin O. Bergo, Donghai Wang
Article
Immunology
Robert F. Stanley, Richard T. Piszczatowski, Boris Bartholdy, Kelly Mitchell, Wendy M. McKimpson, Swathi Narayanagari, Dagmar Walter, Tihomira I. Todorova, Cassandra Hirsch, Hideki Makishima, Britta Will, Christine McMahon, Kira Gritsman, Jaroslaw P. Maciejewski, Richard N. Kitsis, Ulrich Steidl
JOURNAL OF EXPERIMENTAL MEDICINE
(2017)
Review
Oncology
Shayda Hemmati, Tamanna Haque, Kira Gritsman
FRONTIERS IN ONCOLOGY
(2017)
Article
Immunology
Kelly Mitchell, Laura Barreyro, Tihomira I. Todorova, Samuel J. Taylor, Ileana Antony-Debre, Swathi-Rao Narayanagari, Luis A. Carvajal, Joana Leite, Zubair Piperdi, Gopichand Pendurti, Ioannis Mantzaris, Elisabeth Paietta, Amit Verma, Kira Gritsman, Ulrich Steidl
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Medicine, Research & Experimental
Shayda Hemmati, Taneisha Sinclair, Meng Tong, Boris Bartholdy, Rachel O. Okabe, Kristina Ames, Leanne Ostrodka, Tamanna Haque, Imit Kaur, Taylor S. Mills, Anupriya Agarwal, Eric M. Pietras, Jean J. Zhao, Thomas M. Roberts, Kira Gritsman
Article
Hematology
Urvi A. Shah, Elaine Y. Chung, Orsi Giricz, Kith Pradhan, Keisuke Kataoka, Shanisha Gordon-Mitchell, Tushar D. Bhagat, Yun Mai, Yongqiang Wei, Elise Ishida, Gaurav S. Choudhary, Ancy Joseph, Ronald Rice, Nadege Gitego, Crystall Parrish, Matthias Bartenstein, Swati Goel, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Adam Binder, Kira Gritsman, Noah Komblum, Ira Braunschweig, Chirag Bhagat, Jeff Hall, Armin Graber, Lee Ratner, Yanhua Wang, Seishi Ogawa, Amit Verma, B. Hilda Ye, Murali Janakiram
Meeting Abstract
Hematology
Urvi A. Shah, Yanhua Wang, Orsolya Giricz, Shanisha Gordon, Tushar Damodar Bhagat, Yun Mai, Yongqiang Wei, Nadege Gitego, Gaurav Choudhary, Kith Pradhan, Matthias Bartenstein, Ronald Rice, Swati Goel, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Adam F. Binder, Kira Gritsman, Noah Kornblum, Ira Braunschweig, Amit Verma, B. Hilda Ye, Murali Janakiram
Meeting Abstract
Hematology
Diego Adrianzen Herrera, Nilupa Gaspe Mudiyanselage, Pramod Gaudel, Anjali Budhathoki, Karine Darbinyan, Aditi Shastri, Murali Janakiram, Adam F. Binder, Noah Kornblum, Olga Derman, Kira Gritsman, Ulrich G. Steidl, Amit Verma, Ira Braunschweig, Ioannis Mantzaris
Article
Hematology
Karine Darbinyan, Aditi Shastri, Anjali Budhathoki, Daniel Helbig, Rose Snyder, Kith Pradhan, Junaid Saleh-Esa, Noah S. Kornblum, Adam F. Binder, Swati Goel, Murali Janakiram, Olga Derman, Kira Gritsman, Ulrich Steidl, Ira Braunschweig, Amit Verma, Ioannis Mantzaris
Article
Oncology
Tushar D. Bhagat, Si Chen, Matthias Bartenstein, A. Trevor Barlowe, Dagny Von Ahrens, Gaurav S. Choudhary, Patrick Tivnan, Elianna Amin, A. Mario Marcondes, Mathijs A. Sanders, Remco M. Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Iaonnis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafullla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Yeung, Kira Gritsman, Peter Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John M. Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc H. G. P. Raaijmakers, H. Joachim Deeg, Michael G. Kharas, Amit Verma
Meeting Abstract
Hematology
Leanne Ostrodka, Michael Samuel, Taneisha Sinclair, Redwan Bhuiyan, Kira Gritsman
Meeting Abstract
Hematology
Kira Gritsman, Robert P. Hasserjian, Taneisha Sinclair, David M. Weinstock, Britta Will, Ulrich Steidl, Karen K. Ballen, Amir T. Fathi, Amit Verma, Dejan Juric, Philip C. Amrein
Meeting Abstract
Hematology
Kira Gritsman, Imit Kaur, Taneisha Sinclair
