Article
Biochemistry & Molecular Biology
Agnieszka Bochynska, Alexander T. Stenzel, Roksaneh Sayadi Boroujeni, Chao-Chung Kuo, Mirna Barsoum, Weili Liang, Philip Bussmann, Ivan G. Costa, Juliane Luescher-Firzlaff, Bernhard Luescher
Summary: The expression of genes is regulated by the post-translational modifications of core histones. Loss of Ash2l leads to downregulation of H3K4 methylation and gene expression, inhibiting cell proliferation and cell cycle progression, and inducing senescence.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Medicine, Research & Experimental
Tiago Oliveira, Mingfeng Zhang, Eun Ji Joo, Hisham Abdel-Azim, Chun-Wei Chen, Lu Yang, Chih-Hsing Chou, Xi Qin, Jianjun Chen, Kathirvel Alagesan, Andreia Almeida, Francis Jacob, Nicolle H. Packer, Mark von Itzstein, Nora Heisterkamp, Daniel Kolarich
Summary: This study integrated transcriptomics, proteomics and glycomics data to reveal extensive remodeling of glycocalyx in MLL-r cells, identifying potential therapeutic targets and previously unknown protein targets. The research demonstrated the importance of a systematic combined multi-omics approach in providing important diagnostic information that may be missed with a single omics technology.
Article
Dentistry, Oral Surgery & Medicine
X. Zhu, Z. Ma, F. Xie, J. Wang
Summary: The absence of Ash2l resulted in reduced H3K4me3 modification, leading to abnormal morphology of dental germ and impaired enamel and dentin formation. Ash2l knockout also disrupted the expression of crucial genes such as Shh and Trp63, leading to aberrant differentiation, proliferation, and apoptosis of the dental epithelium.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Oncology
Xiao-Na Zhu, Yu-Sheng Wei, Qian Yang, Hao-Ran Liu, Zhe Zhi, Di Zhu, Li Xia, Deng-Li Hong, Yun Yu, Guo-Qiang Chen
Summary: In this study, it was found that FBXO22 is highly expressed in MLLr AML and promotes AML progression by targeting BACH1 for degradation. Knockdown of FBXO22 leads to increased apoptosis in MLLr leukemia cells and reduced LSCs in serial transplantations. Targeting FBXO22 could be an ideal strategy to eradicate LSCs without affecting normal hematopoiesis.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Antonella Di Mambro, Yoana Arroyo-Berdugo, Tiziana Fioretti, Michael Randles, Luca Cozzuto, Vinothini Rajeeve, Armando Cevenini, Michael J. Austin, Gabriella Esposito, Julia Ponomarenko, Claire M. Lucas, Pedro Cutillas, John Gribben, Owen Williams, Yolanda Calle, Bela Patel, Maria Teresa Esposito
Summary: This study reveals the essential role and underlying mechanisms of the endogenous phosphatase inhibitor SET in KMT2A-rearranged (KMT2A-R) leukemia, and suggests that SET antagonism could serve as a novel strategy to treat this aggressive leukemia.
Article
Multidisciplinary Sciences
Mirna Barsoum, Alexander T. Stenzel, Agnieszka Bochynska, Chao-Chung Kuo, Alexander Tsompanidis, Roksaneh Sayadi-Boroujeni, Philip Bussmann, Juliane Luescher-Firzlaff, Ivan G. Costa, Bernhard Luescher
Summary: This study investigates the impact of Ash2l loss on gene expression and cellular function. The results indicate that Ash2l loss leads to a decrease in H3K4me3 and changes in chromatin accessibility, affecting gene transcription and cellular function.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Giuseppe Zardo
Summary: CpG methylation plays vital roles in gene regulation, with CpG islands in promoters remaining unmethylated throughout mammalian embryogenesis and development. Understanding the mechanisms and effects of aberrant CpG island hypermethylation in tumors requires further investigation.
Review
Oncology
Tiffany M. Tran, Dinesh S. Rao
Summary: RNA binding proteins (RBPs) have emerged as important regulators of post-transcriptional gene expression, influencing mRNA fate through multiple mechanisms and critically impacting oncogenic transcript expression. This article focuses on the major features and mechanisms of RBPs, and discusses the current progress in investigating the function of important RBPs in MLL-rearranged leukemia.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mark Kerstjens, Patricia Garrido Castro, Sandra S. Pinhancos, Pauline Schneider, Priscilla Wander, Rob Pieters, Ronald W. Stam
Summary: Acute lymphoblastic leukemia (ALL) in infants involving MLL gene translocations accounts for about 80% of cases, with poor prognoses under current chemotherapeutic regimens. Through in vitro drug screening, Camptothecin and its derivatives showed potent effects on ALL cell lines. Further study revealed that Irinotecan, a pro-drug of SN-38, exhibited strong anti-leukemia effects against pediatric MLL-rearranged ALL.
Article
Medicine, Research & Experimental
Juan Ramon Tejedor, Clara Bueno, Meritxell Vinyoles, Paolo Petazzi, Antonio Agraz-Doblas, Isabel Cobo, Raul Torres-Ruiz, Gustavo F. Bayon, Raul F. Perez, Sara Lopez-Tamargo, Francisco Gutierrez-Aguera, Pablo Santamarina-Ojeda, Manuel Ramirez-Orellana, Michela Bardini, Giovanni Cazzaniga, Paola Ballerini, Pauline Schneider, Ronald W. Stam, Ignacio Varela, Mario F. Fraga, Agustin F. Fernandez, Pablo Menendez
Summary: B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with infant B-ALL (iB-ALL) showing unique DNA mutational landscape and potential epigenetic mechanisms contributing to leukemogenesis. Integrated analysis of methylome and transcriptome data from MLLr and non-MLLr iB-ALL patients revealed chromatin state alterations and identified distinct gene expression patterns, particularly related to the AP-1 complex and RUNX factors in MLLr iB-ALL. Pharmacological inhibition of AP-1 showed promising potential in impairing MLLr-leukemic growth, suggesting a novel therapeutic approach for MLLr-iB-ALL.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Klaudyna Fidyt, Agata Pastorczak, Julia Cyran, Nicholas T. Crump, Agnieszka Goral, Joanna Madzio, Angelika Muchowicz, Martyna Poprzeczko, Krzysztof Domka, Lukasz Komorowski, Magdalena Winiarska, Joe R. Harman, Karolina Siudakowska, Agnieszka Graczyk-Jarzynka, Elzbieta Patkowska, Ewa Lech-Maranda, Wojciech Mlynarski, Jakub Golab, Thomas A. Milne, Malgorzata Firczuk
Summary: This study reveals the potential mechanisms underlying limited activity of venetoclax in MLLr BCP-ALL and identifies auranofin as a sensitizer for venetoclax, independently of the p53 pathway. Auranofin enhances the sensitivity of MLLr BCP-ALL to venetoclax by upregulating the NOXA pro-apoptotic protein and inducing apoptotic cell death. These findings suggest a potential effective drug combination for the treatment of MLLr BCP-ALL patients.
Article
Multidisciplinary Sciences
Young-Tae Lee, Alex Ayoub, Sang-Ho Park, Liang Sha, Jing Xu, Fengbiao Mao, Wei Zheng, Yang Zhang, Uhn-Soo Cho, Yali Dou
Summary: This study demonstrates how the intrinsically disordered regions of ASH2L and DPY30 restrict the rotational dynamics of MLL1 on the nucleosome core particle, leading to more efficient enzyme-substrate engagement and higher H3K4 trimethylation activity.
NATURE COMMUNICATIONS
(2021)
Article
Biology
William F. Richter, Rohan N. Shah, Alexander J. Ruthenburg
Summary: Research shows that MLL-rearranged leukemia depends on H3K79 methylation, with depletion of this mark downregulating key genes and alternative proliferation pathways. Low-dose pinometostat specifically targets FLT3 transcription, providing a potential treatment strategy for FLT3-mutant leukemia.
Article
Biochemistry & Molecular Biology
Lulu Liu, Lingling Shen, Zhilou Ding, Miao He, En Li, John A. Tallarico, Rishi K. Jain, He Wang
Summary: Drug resistance is a major problem in targeted cancer therapy that can be caused by mutations or activation of bypass signaling pathways. WDR5 has been identified as a potential drug target due to its multifaceted function in cancer. This study found that cancer cells can develop resistance to a powerful WDR5 inhibitor through a specific mutation, providing insights into the resistance mechanism for future clinical research.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jacqueline Fischer, Estelle Erkner, Rahel Fitzel, Pia Radszuweit, Hildegard Keppeler, Fulya Korkmaz, Giovanni Roti, Claudia Lengerke, Dominik Schneidawind, Corina Schneidawind
Summary: The NOTCH1 pathway plays an important role in the pathogenesis of MLLr leukemia and its inhibition can lead to specific anti-leukemic effects, providing potential for further evaluation in clinical settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)