Article
Biotechnology & Applied Microbiology
Sisi Li, Zhujun Wang, Xiaoping Guo, Ping Chen, Yongmin Tang
Summary: In this study, a novel immunotoxin, Hm3A4-Rap, targeting leukemia stem cells in AML, was generated and shown to have excellent biological activity, indicating its potential therapeutic value for treating AML patients.
Review
Cell Biology
Narissa Parry, Helen Wheadon, Mhairi Copland
Summary: The BCL-2 proteins play a crucial role in regulating the intrinsic apoptotic pathway by balancing the prosurvival and proapoptotic members to activate BAX and BAK. Small molecule inhibitors targeting prosurvival proteins, known as 'BH3 mimetics,' have become an important approach in treating hematological malignancies, with the BCL-2-specific inhibitor Venetoclax showing significant success in AML treatment. As research into utilizing BH3 mimetics in myeloid leukemia treatment continues to expand, evaluating the current position in this field is increasingly important.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Marion Polomski, Marie Brachet-Botineau, Ludovic Juen, Marie-Claude Viaud-Massuard, Fabrice Gouilleux, Gildas Prie
Summary: The researchers synthesized analogs of molecule 17 f and found two compounds, 7 a and 7 a', to have higher antileukemic effects in AML and CML cell lines, demonstrating more efficient inhibition of STAT5 activity/expression and chemoresistance compared to 17 f.
Review
Oncology
Julian Swatler, Laura Turos-Korgul, Ewa Kozlowska, Katarzyna Piwocka
Summary: Effector immune system cells have the ability to kill tumor cells, but they are inhibited and evaded as myeloid leukemias develop. Factors such as inhibitory receptors, enzymes and suppressive immune cells contribute to the immunosuppressive microenvironment. Changes in immunosuppressive features during therapy include modulation of cytotoxic cells, promotion of regulatory T cells and suppressive myeloid cells, and spreading of leukemic blasts. Treatment modalities such as tyrosine kinase inhibitors and chemotherapy aim to restore effector immunity in myeloid leukemias.
Article
Cell Biology
Gagandeep Singh, Neelam Thakur, Umesh Kumar
Summary: This article discusses how understanding the circuitry of RAS can help develop effective therapeutic strategies against RAS-driven malignancies.
CELLULAR SIGNALLING
(2023)
Review
Oncology
Matthieu Duchmann, Lucie Laplane, Raphael Itzykson
Summary: The text discusses the genetic and epigenetic alterations underlying acute myeloid leukemias and the intratumoral diversity of leukemic cells. It highlights the importance of understanding AML as an evolutionary process for developing novel therapeutic strategies. The impact of clonal diversity on patient outcomes and the mechanisms driving clonal dynamics are also emphasized.
Review
Oncology
Aboli Bhingarkar, Hima V. Vangapandu, Sanjay Rathod, Keito Hoshitsuki, Christian A. Fernandez
Summary: The metabolism of amino acids plays a crucial role in cellular processes, especially in cancer cells that require increased amino acid uptake for energy production. This review focuses on the dysregulation of biosynthetic enzymes in myeloid leukemias and the impact of GCN2 and mTOR pathways on metabolic vulnerability and drug resistance.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Lei Lin, Lei Miao, Huiran Lin, Jiwen Cheng, Meng Li, Zhenjian Zhuo, Jing He
Summary: Neuroblastoma is a common solid tumor in children that poses challenges to current therapies. Personalized treatment and new therapies targeting RAS mutations hold promise for improving treatment outcomes. This review article focuses on the biological role and frequency of RAS mutations in neuroblastoma, as well as the strategies and progress in targeting RAS in preclinical and clinical settings, and discusses possible future prospects and challenges.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Ugo Testa, Elvira Pelosi, Germana Castelli
Summary: The current classification of acute myeloid leukemia (AML) relies on genomic alterations. AML with mutated nucleophosmin 1 (NPM1-mut) is the largest genetically defined group, accounting for about 30% of adult AMLs and is recognized as a distinct entity in the current AML classifications. NPM1-mut AML is usually associated with a normal karyotype and relatively favorable prognosis, but it is genetically, transcriptionally, and phenotypically heterogeneous. Recent studies highlight the need for additional stratification to improve therapeutic response for different subgroups of NPM1-mut AML patients.
Article
Chemistry, Multidisciplinary
Jing Xu, Ailing Zhong, Shan Zhang, Mei Chen, Lanxin Zhang, Xiaohang Hang, Jianan Zheng, Baohong Wu, Xintong Deng, Xiangyu Pan, Zhongwang Wang, Lu Qi, Kaidou Shi, Shujun Li, Yiyun Wang, Manli Wang, Xuelan Chen, Qi Zhang, Pengpeng Liu, Robert Peter Gale, Chong Chen, Yu Liu, Ting Niu
Summary: KMT2C and KMT2D are frequently mutated genes in human cancers, with KMT2C identified as a tumor suppressor in acute myeloid leukemia (AML). The role of KMT2D in AML has remained unclear, but this study shows that its downregulation or mutation accelerates leukemogenesis in mice. KMT2D deficiency leads to enhanced ribosome biogenesis and the activation of the mTOR pathway in AML cells, suggesting a vulnerability to ribosome biogenesis inhibition.
Review
Oncology
Luca Guarnera, Tiziana Ottone, Emiliano Fabiani, Mariadomenica Divona, Arianna Savi, Serena Travaglini, Giulia Falconi, Paola Panetta, Maria Cristina Rapanotti, Maria Teresa Voso
Summary: APL, a subtype of AML, has a favorable prognosis thanks to ATRA and ATO combination therapy, but some cases caused by atypical transcripts have variable response rates to treatment, posing a challenge for clinical management.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Yan Yi, Shenglei Ge
Summary: This article reviews the recent advances and future trends of therapeutic strategies against DOT1L for MLL-rearranged leukemias, and discusses the limitations, challenges, and prospects of these strategies. DOT1L, as a therapeutic target for MLL-rearranged leukemias, holds important research and development value.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Jayastu Senapati, Naval G. Daver, Naveen Pemmaraju
Summary: Targeted therapy with antibody-drug conjugates (ADCs) has shown promise in maximizing cancer cell cytotoxicity with minimal off-target effects. ADCs have been used in the treatment of specific subtypes of leukemia, leading to improved response rates and outcomes. Further research is being conducted to identify novel cellular targets and improve delivery of cytotoxic agents using ADCs.
Article
Oncology
Yan Zi Au, Muxin Gu, Etienne De Braekeleer, Malgorzata Gozdecka, Demetrios Aspris, Yusuke Tarumoto, Jonathan Cooper, Jason Yu, Swee Hoe Ong, Xi Chen, Konstantinos Tzelepis, Brian J. P. Huntly, George Vassiliou, Kosuke Yusa
Summary: The study identifies the importance of KAT7 in AML, showing that its loss leads to the loss of related marks and affects proliferation and differentiation of AML cells. The acetyltransferase activity of KAT7 is crucial for cell proliferation, making it a potential therapeutic target for this subtype of AML with poor prognosis.
Review
Pharmacology & Pharmacy
Yuran Qiu, Yuanhao Wang, Zongtao Chai, Duan Ni, Xinyi Li, Jun Pu, Jie Chen, Jian Zhang, Shaoyong Lu, Chuan Lv, Mingfei Ji
Summary: RAS is a key oncogenic protein, and mutations in it can lead to human cancer. Recent studies have identified several phosphorylation residues in RAS protein that can regulate its activity, providing a new direction for developing anti-RAS drugs. This review summarizes the research advances in RAS phosphorylation and provides insights into therapeutic strategies.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
E. J. Pomeroy, L. A. Lee, R. D. W. Lee, D. K. Schirm, N. A. Temiz, J. Ma, T. A. Gruber, E. Diaz-Flores, B. S. Moriarity, J. R. Downing, K. M. Shannon, D. A. Largaespada, C. E. Eckfeldt
Article
Hematology
Jin Xu, Christian Hedberg, Frank J. Dekker, Qing Li, Kevin M. Haigis, Eugene Hwang, Herbert Waldmann, Kevin Shannon
Article
Hematology
Angell Shieh, Ashley F. Ward, Kegan L. Donlan, Emily R. Harding-Theobald, Jin Xu, Charles G. Mullighan, Chao Zhang, Shann-Ching Chen, Xiaoping Su, James R. Downing, Gideon E. Bollag, Kevin M. Shannon
Letter
Hematology
Elliot Stieglitz, Y. Lucy Liu, Peter D. Emanuel, Robert P. Castleberry, Todd M. Cooper, Kevin M. Shannon, Mignon L. Loh
Editorial Material
Hematology
Kevin Shannon, Michelle Hermiston
Article
Hematology
Zohar Sachs, Rebecca S. LaRue, Hanh T. Nguyen, Karen Sachs, Klara E. Noble, Nurul Azyan Mohd Hassan, Ernesto Diaz-Flores, Susan K. Rathe, Aaron L. Sarver, Sean C. Bendall, Ngoc A. Ha, Miechaleen D. Diers, Garry P. Nolan, Kevin M. Shannon, David A. Largaespada
Article
Hematology
Michael R. Burgess, Eugene Hwang, Ari J. Firestone, Tannie Huang, Jin Xu, Johannes Zuber, Natacha Bohin, Tiffany Wen, Scott C. Kogan, Kevin M. Haigis, Deepak Sampath, Scott Lowe, Kevin Shannon, Qing Li
Article
Oncology
Chong Chen, Yu Liu, Amy R. Rappaport, Thomas Kitzing, Nikolaus Schultz, Zhen Zhao, Aditya S. Shroff, Ross A. Dickins, Christopher R. Vakoc, James E. Bradner, Wendy Stock, Michelle M. LeBeau, Kevin M. Shannon, Scott Kogan, Johannes Zuber, Scott W. Lowe
Article
Medicine, Research & Experimental
Tiffany Chang, Kimberly Krisman, Emily Harding Theobald, Jin Xu, Jon Akutagawa, Jennifer O. Lauchle, Scott Kogan, Benjamin S. Braun, Kevin Shannon
JOURNAL OF CLINICAL INVESTIGATION
(2013)
Article
Multidisciplinary Sciences
Li Ding, Timothy J. Ley, David E. Larson, Christopher A. Miller, Daniel C. Koboldt, John S. Welch, Julie K. Ritchey, Margaret A. Young, Tamara Lamprecht, Michael D. McLellan, Joshua F. McMichael, John W. Wallis, Charles Lu, Dong Shen, Christopher C. Harris, David J. Dooling, Robert S. Fulton, Lucinda L. Fulton, Ken Chen, Heather Schmidt, Joelle Kalicki-Veizer, Vincent J. Magrini, Lisa Cook, Sean D. McGrath, Tammi L. Vickery, Michael C. Wendl, Sharon Heath, Mark A. Watson, Daniel C. Link, Michael H. Tomasson, William D. Shannon, Jacqueline E. Payton, Shashikant Kulkarni, Peter Westervelt, Matthew J. Walter, Timothy A. Graubert, Elaine R. Mardis, Richard K. Wilson, John F. DiPersio
Article
Multidisciplinary Sciences
Qing Li, Natacha Bohin, Tiffany Wen, Victor Ng, Jeffrey Magee, Shann-Ching Chen, Kevin Shannon, Sean J. Morrison
Article
Multidisciplinary Sciences
Monique Dail, Jason Wong, Jessica Lawrence, Daniel O'Connor, Joy Nakitandwe, Shann-Ching Chen, Jin Xu, Leslie B. Lee, Keiko Akagi, Qing Li, Jon C. Aster, Warren S. Pear, James R. Downing, Deepak Sampath, Kevin Shannon
Article
Biochemistry & Molecular Biology
Ernesto Diaz-Flores, Hana Goldschmidt, Philippe Depeille, Victor Ng, Jon Akutagawa, Kimberly Krisman, Michael Crone, Michael R. Burgess, Olusegun Williams, Benjamin Houseman, Kevan Shokat, Deepak Sampath, Gideon Bollag, Jeroen P. Roose, Benjamin S. Braun, Kevin Shannon
Article
Biochemistry & Molecular Biology
Catherine Hartzell, Olga Ksionda, Ed Lemmens, Kristen Coakley, Ming Yang, Monique Dail, Richard C. Harvey, Christopher Govern, Jeroen Bakker, Tineke L. Lenstra, Kristin Ammon, Anne Boeter, Stuart S. Winter, Mignon Loh, Kevin Shannon, Arup K. Chakraborty, Matthias Wabl, Jeroen P. Roose
Article
Oncology
Jin Xu, Kevin M. Haigis, Ari J. Firestone, Megan E. McNerney, Qing Li, Elizabeth Davis, Shann-Ching Chen, Joy Nakitandwe, James Downing, Tyler Jacks, Michelle M. Le Beau, Kevin Shannon