Review
Hematology
Sushanta Kumar Mishra, Scott E. Millman, Lingbo Zhang
Summary: Metabolic rewiring and cellular reprogramming are characteristic features of neoplastic initiation and progression in AML. Targeting abnormal metabolic activities provides therapeutic opportunities with improved efficacy and wider therapeutic windows.
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Article
Multidisciplinary Sciences
Qianze Dong, Yan Xiu, Yang Wang, Christina Hodgson, Nick Borcherding, Craig Jordan, Jane Buchanan, Eric Taylor, Brett Wagner, Mariah Leidinger, Carol Holman, Dennis J. Thiele, Sean O'Brien, Hai-hui Xue, Jinming Zhao, Qingchang Li, Howard Meyerson, Brendan F. Boyce, Chen Zhao
Summary: The transcription factor HSF1 is specifically required for the maintenance of leukemia stem cells in acute myeloid leukemia (AML), and pharmacologically targeting HSF1 may have broad anti-leukemic effects.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Lais Ghiraldeli, Rebecca Anderson, Kristin Pladna, Timothy S. Pardee
Summary: Adenosine monophosphate activated protein kinase (AMPK) plays an important role in chemotherapy response in acute myeloid leukemia (AML). Knocking out AMPK activity in AML cells results in significant resistance to chemotherapy drugs and is associated with shorter survival in patients with low expression of AMPK subunit. Additionally, sensitizing AML cells to chemotherapy can be achieved by activating AMPK.
Review
Biochemistry & Molecular Biology
Hanyun Zhang, Chunjie Sun, Qi Sun, Ye Li, Chao Zhou, Changgang Sun
Summary: This study summarizes recent studies on ferroptosis in AML cells, highlighting the increased susceptibility of AML cells to ferroptosis due to their metabolic characteristics, gene mutation patterns, and dependence on mitochondria. The study also summarizes the strategies used by AML cells to evade ferroptosis and the drugs targeting the ferroptosis pathway in AML treatment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Immunology
Xiqin Tong, Fuling Zhou
Summary: This study analyzed the mutation status of 31 mitochondrial metabolism-related genes in AML patients and constructed a prognosis model based on five genes, which accurately distinguished high-risk and low-risk patients. It was also found that high-risk patients had more immune-cell infiltration and poor immunotherapy response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Bo Jiang, Junyuan Qi, Mingyuan Sun, Weiwei Zheng, Yongyue Wei, Jianxiang Wang, Fengkui Zhang
Summary: This study evaluated the pharmacokinetic profiles of flumatinib mesylate tablets at doses of 400 mg and 600 mg in patients with CML-CP. The results showed that flumatinib exposure increased in an approximately dose-proportional manner, with slow elimination and manageable adverse events. Further research is needed in a larger sample size study.
FRONTIERS IN ONCOLOGY
(2023)
Article
Genetics & Heredity
Fangshu Liu, Suqi Deng, Yue Li, Juan Du, Hui Zeng
Summary: In this study, the researchers found that the high expression level of SLC25A1 gene in AML patients is associated with unfavorable prognosis. They further demonstrated that inhibition of SLC25A1 can inhibit the proliferation and increase the apoptosis of AML cells. By constructing a SLC25A1-associated gene panel, they established a prognostic risk-scoring model that can be used as an independent biomarker to assess prognosis in AML.
FRONTIERS IN GENETICS
(2023)
Article
Hematology
Geoffrey L. Uy, Ibrahim Aldoss, Matthew C. Foster, Peter H. Sayre, Matthew J. Wieduwilt, Anjali S. Advani, John E. Godwin, Martha L. Arellano, Kendra L. Sweet, Ashkan Emadi, Farhad Ravandi, Harry P. Erba, Michael Byrne, Laura Michaelis, Max S. Topp, Norbert Vey, Fabio Ciceri, Matteo Giovanni Carrabba, Stefania Paolini, Gerwin A. Huls, Mojca Jongen-Lavrencic, Martin Wermke, Patrice Chevallier, Emmanuel Gyan, Christian Recher, Patrick J. Stiff, Kristen M. Pettit, Bob Lowenberg, Sarah E. Church, Erica Anderson, Jayakumar Vadakekolathu, Marianne Santaguida, Michael P. Rettig, John Muth, Teia Curtis, Erin Fehr, Kuo Guo, Jian Zhao, Ouiam Bakkacha, Kenneth Jacobs, Kathy Tran, Patrick Kaminker, Maya Kostova, Ezio Bonvini, Roland B. Walter, Jan K. Davidson-Moncada, Sergio Rutella, John F. DiPersio
Summary: This study presents the results of a multicenter, open-label, phase 1/2 study of flotetuzumab in 88 adults with relapsed/refractory AML, showing clinical benefits in PIF/ER patients and encouraging evidence of activity. Flotetuzumab represents an innovative experimental approach associated with acceptable safety.
Review
Oncology
Michael Loschi, Pierre Fenaux, Thomas Cluzeau
Summary: TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by poor prognosis. In this review, we analyze the prognosis of these diseases, focusing on the extent of TP53 mutation status and its correlation with cytogenetic complexity. We discuss the potential improvement in outcome based on recent results obtained with new drugs (especially eprenetapopt and magrolimab). The impact of allogeneic hematopoietic stem cell transplantation (aHSCT) and post-transplantation treatment is also emphasized.
Article
Immunology
Mahnaz Rezaei, Mustafa Ghanadian, Behrooz Ghezelbash, Abolfazl Shokouhi, Alexandr V. Bazhin, Andrey A. Zamyatnin Jr, Mazdak Ganjalikhani-Hakemi
Summary: The study reveals that the interaction between TIM-3 and Gal-9 in AML cell lines leads to aerobic glycolysis and altered lipid metabolism, while also protecting cells from oxidative stress, thus promoting leukemic cell survival and proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Rebecca Anderson, Kristin M. Pladna, Nathaniel J. Schramm, Frances B. Wheeler, Steven Kridel, Timothy S. Pardee
Summary: Acute myeloid leukemia (AML) is an aggressive and therapy-resistant disease. Devimistat, a novel agent that inhibits pyruvate dehydrogenase complex, did not show any benefit in a phase III clinical trial for AML patients. AML cells were able to circumvent the metabolic inhibition of devimistat. Understanding the mechanisms by which AML cells resist metabolic inhibition can lead to the development of new approaches.
Article
Biochemistry & Molecular Biology
Timothy A. Yap, Naval Daver, Mikhila Mahendra, Jixiang Zhang, Carlos Kamiya-Matsuoka, Funda Meric-Bernstam, Hagop M. Kantarjian, Farhad Ravandi, Meghan E. Collins, Maria Emilia Di Francesco, Ecaterina E. Dumbrava, Siqing Fu, Sisi Gao, Jason P. Gay, Sonal Gera, Jing Han, David S. Hong, Elias J. Jabbour, Zhenlin Ju, Daniel D. Karp, Alessia Lodi, Jennifer R. Molina, Natalia Baran, Aung Naing, Maro Ohanian, Shubham Pant, Naveen Pemmaraju, Prithviraj Bose, Sarina A. Piha-Paul, Jordi Rodon, Carolina Salguero, Koji Sasaki, Anand K. Singh, Vivek Subbiah, Apostolia M. Tsimberidou, Quanyun A. Xu, Musa Yilmaz, Qi Zhang, Yuan Li, Christopher A. Bristow, Meenakshi B. Bhattacharjee, Stefano Tiziani, Timothy P. Heffernan, Christopher P. Vellano, Philip Jones, Cobi J. Heijnen, Annemieke Kavelaars, Joseph R. Marszalek, Marina Konopleva
Summary: Despite being a rational anticancer strategy, targeting OXPHOS with inhibitors has not yet shown clinical benefit. Two phase I trials of IACS-010759, a potent and selective complex I inhibitor, were conducted in patients with relapsed/refractory acute myeloid leukemia and advanced solid tumors. However, dose-limiting toxicities and limited antitumor activity were observed, leading to the discontinuation of both trials.
Review
Oncology
Lili Feng, Philip Y. Zhang, Wenda Gao, Jinming Yu, Simon C. Robson
Summary: Chemoresistance is a complex issue in cancer management, particularly in cases of acute myeloid leukemia (AML). Mitochondrial function plays a crucial role in the viability and chemoresistance of AML cells. Targeting specific elements of abnormal mitochondrial metabolism could be an effective therapeutic strategy in leukemia. Mitotherapy, which aims to override mitochondria-mediated metabolic reprogramming in cancer cells, may be a complementary approach to overcome chemoresistance in liquid cancers and solid tumors.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Fei Han, Huanhuan Zhao, Jun Lu, Weina Yun, Lingling Yang, Yude Lou, Dan Su, Xin Chen, Shixuan Zhang, Hanwei Jin, Xiang Li, Jie Sun, He Huang, Qishan Wang, Xi Jiang
Summary: This study found that the downregulation of BDH1 gene expression in acute myeloid leukemia (AML) is associated with worse prognosis, and overexpression of BDH1 inhibits the viability and proliferation of AML cells.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Michele Maio, Arnaud Scherpereel, Luana Calabro, Joachim Aerts, Susana Cedres Perez, Alessandra Bearz, Kristiaan Nackaerts, Dean A. Fennell, Dariusz Kowalski, Anne S. Tsao, Paul Taylor, Federica Grosso, Scott J. Antonia, Anna K. Nowak, Maria Taboada, Martina Puglisi, Paul K. Stockman, Hedy L. Kindler
Article
Oncology
Elinor A. Chapman, Melanie Oates, Ishaque S. Mohammad, Barry R. Davies, Paul K. Stockman, Jianguo Zhuang, Andrew R. Pettitt
Article
Oncology
D. S. Boss, P. O. Witteveen, J. van der Sar, M. P. Lolkema, E. E. Voest, P. K. Stockman, O. Ataman, D. Wilson, S. Das, J. H. Schellens
ANNALS OF ONCOLOGY
(2011)
Article
Hematology
Bob Lowenberg, Petra Muus, Gert Ossenkoppele, Philippe Rousselot, Jean-Yves Cahn, Norbert Ifrah, Giovanni Martinelli, Sergio Amadori, Ellin Berman, Pieter Sonneveld, Mojca Jongen-Lavrencic, Sophie Rigaudeau, Paul Stockman, Alison Goudie, Stefan Faderl, Elias Jabbour, Hagop Kantarjian
Article
Oncology
Hagop M. Kantarjian, Giovanni Martinelli, Elias J. Jabbour, Alfonso Quintas-Cardama, Kiyoshi Ando, Jacques-Olivier Bay, Andrew Wei, Stefanie Groepper, Cristina Papayannidis, Kate Owen, Laura Pike, Nicola Schmitt, Paul K. Stockman, Aristoteles Giagounidis
Article
Oncology
Hagop M. Kantarjian, Mikkael A. Sekeres, Vincent Ribrag, Philippe Rousselot, Guillermo Garcia-Manero, Elias J. Jabbour, Kate Owen, Paul K. Stockman, Stuart D. Oliver
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2013)
Article
Oncology
Gary K. Schwartz, Richard D. Carvajal, Rachel Midgley, Scott J. Rodig, Paul K. Stockman, Ozlem Ataman, David Wilson, Shampa Das, Geoffrey I. Shapiro
INVESTIGATIONAL NEW DRUGS
(2013)
Article
Oncology
Ronald B. Natale, David Bodkin, Ramaswamy Govindan, Bethany G. Sleckman, Naiyer A. Rizvi, Adolfo Capo, Paul Germonpre, Wilfried E. E. Eberhardt, Paul K. Stockman, Sarah J. Kennedy, Malcolm Ranson
JOURNAL OF CLINICAL ONCOLOGY
(2009)
Article
Medicine, Research & Experimental
Paul Baverel, Lorin Roskos, Manasa Tatipalli, Nancy Lee, Paul Stockman, Maria Taboada, Paolo Vicini, Kevin Horgan, Rajesh Narwal
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2019)
Article
Oncology
E. Van Cutsem, Y. -J. Bang, W. Mansoor, R. D. Petty, Y. Chao, D. Cunningham, D. R. Ferry, N. R. Smith, P. Frewer, J. Ratnayake, P. K. Stockman, E. Kilgour, D. Landers
ANNALS OF ONCOLOGY
(2017)