Article
Multidisciplinary Sciences
Morten Tulstrup, Mette Soerensen, Jakob Werner Hansen, Linn Gillberg, Maria Needhamsen, Katja Kaastrup, Kristian Helin, Kaare Christensen, Joachim Weischenfeldt, Kirsten Gronbaek
Summary: TET2 mutations are associated with hypermethylated enhancers involved in myeloid differentiation in both CHIP, CCUS and AML patients. These hypermethylated sites are associated with leukocyte function, immune response, as well as ETS-related and C/EBP-related transcription factor motifs.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Lashanale Wallace, Esther A. Obeng
Summary: Hematopoiesis is a crucial process for organismal development and homeostasis, and epigenetic regulation plays a critical role in normal hematopoiesis. Imbalance between self-renewal and cell fate decisions can lead to hematologic diseases, and targeted therapies against epigenetic regulators have shown promising outcomes in hematological malignancy.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Lars Velten, Benjamin A. Story, Pablo Hernandez-Malmierca, Simon Raffel, Daniel R. Leonce, Jennifer Milbank, Malte Paulsen, Aykut Demir, Chelsea Szu-Tu, Robert Fromel, Christoph Lutz, Daniel Nowak, Johann-Christoph Jann, Caroline Pabst, Tobias Boch, Wolf-Karsten Hofmann, Carsten Muller-Tidow, Andreas Trumpp, Simon Haas, Lars M. Steinmetz
Summary: This study successfully identified and molecularly profiled LSCs, HSCs, and pre-leukemic stem cells in AML by combining single-cell transcriptomics and lineage tracing techniques.
NATURE COMMUNICATIONS
(2021)
Article
Environmental Sciences
Hong-qiang Chen, Dong-jiao Chen, Yan Li, Fei Han, Xiao Jiang, Jia Cao, Jin-yi Liu, Wen-bin Liu
Summary: The study successfully established a model of 3-MCA-induced malignant transformation of HBE cells, revealing key genes involved in lung carcinogenesis through processes such as cell growth, migration, and invasion. Gene expression and DNA methylation and hydroxymethylation play important roles in environmental 3-MCA-induced lung carcinogenesis.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Cell Biology
Raghav Ramabadran, Jarey H. Wang, Jaime M. Reyes, Anna G. Guzman, Sinjini Gupta, Carina Rosas, Lorenzo Brunetti, Michael C. Gundry, Ayala Tovy, Hali Long, Tianpeng Gu, Sean M. Cullen, Siddhartha Tyagi, Danielle Rux, Jean J. Kim, Steven M. Kornblau, Michael Kyba, Fabio Stossi, Rachel E. Rau, Koichi Takahashi, Thomas F. Westbrook, Margaret A. Goodell
Summary: Ramabadran et al. discovered that upon extrinsic stimulation, stem cells activate a program involving increased splicing efficiency mediated by DNMT3A and recruitment of SF3B1 to RNA polymerase and mRNA, promoting the activation of embryonic and hematopoietic stem cells. This DNA methylation-independent role of DNMT3A in stem cell activation and splicing regulation provides new insights into the mechanisms governing stem cell differentiation.
NATURE CELL BIOLOGY
(2023)
Article
Oncology
Kuangguo Zhou, Mi Zhou, Ling Cheng, Xing Chen, Xiaomin Wang, Yajing Chu, Qilin Yu, Shu Zhang, Na Wang, Lei Zhao, Di Wang, Liang Huang, Congyi Wang, Weiping Yuan, Jianfeng Zhou
Summary: MBD2 plays a role in promoting AML development by modulating gene expression related to myeloid differentiation and sustaining the oncogenic gene program. Targeting MBD2 could potentially be a therapeutic strategy for myeloid malignancies.
Article
Medicine, Research & Experimental
Amy C. Fan, Yusuke Nakauchi, Lawrence Bai, Armon Azizi, Kevin A. Nuno, Feifei Zhao, Thomas Koehnke, Daiki Karigane, David Cruz-Hernandez, Andreas Reinisch, Purvesh Khatri, Ravindra Majeti
Summary: This study reveals the dependence of RUNX1-mutant leukemias on IL-3/JAK/STAT signaling, which can potentially be targeted using JAK inhibitors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Ningfei An, Saira Khan, Molly K. K. Imgruet, Lia Jueng, Sandeep Gurbuxani, Megan E. E. McNerney
Summary: -7/del(7q) is commonly found in myeloid neoplasms. CUX1, located on 7q22, is a transcription factor associated with poor prognosis when mutated. CUX1 deficiency and oncogenic RAS mutations are found to be linked and promote leukemogenesis. This research indicates a potential therapy for malignancies with CUX1 inactivation.
Article
Multidisciplinary Sciences
Zaka Wing-Sze Yuen, Akanksha Srivastava, Runa Daniel, Dennis McNevin, Cameron Jack, Eduardo Eyras
Summary: The study evaluated the performance of multiple tools in detecting CpG methylation from Nanopore sequencing, revealing a tradeoff between false positives and false negatives. The authors proposed a consensus approach, METEORE, to improve prediction accuracy, and provided Snakemake pipelines for reproducibility.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Agostina Bianchi, Michael Scherer, Roser Zaurin, Kimberly Quililan, Lars Velten, Renee Beekman
Summary: In this study, a high-throughput and high-confidence method called scTAM-seq was developed for analyzing DNA methylation in single cells. It can profile thousands of single cells and resolve DNA methylation dynamics during cell differentiation.
Editorial Material
Cell Biology
Paul B. Talbert, Steven Henikoff
Summary: The conserved chromatin remodeller DDM1 has been a puzzle due to its indirect effect in maintaining plant DNA methylation. However, a recent study shows that DDM1 directly deposits the H2A.W histone variant to silence transposable elements.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Alexandre T. Vessoni, Tianpeng Zhang, Annabel Quinet, Ho-Chang Jeong, Michael Munroe, Matthew Wood, Enzo Tedone, Alessandro Vindigni, Jerry W. Shay, Roger A. Greenberg, Luis F. Z. Batista
Summary: It has been shown that telomere shortening in human pluripotent stem cells leads to single-stranded DNA accumulation, unique cell cycle abnormalities, and increased mitotic issues. Loss of p53 increases resistance to death but also results in more mitotic abnormalities. The unexpected dominant role of ATR in hPSCs demonstrates consequences distinct from their differentiated counterparts.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Oncology
Kei Mizuno, Takayuki Sumiyoshi, Takatsugu Okegawa, Naoki Terada, Satoshi Ishitoya, Yu Miyazaki, Takahiro Kojima, Hiromichi Katayama, Naohiro Fujimoto, Shingo Hatakeyama, Masaki Shiota, Koji Yoshimura, Yoshiyuki Matsui, Shintaro Narita, Hiroaki Matsumoto, Ryoma Kurahashi, Hidenori Kanno, Katsuhiro Ito, Hiroko Kimura, Yuki Kamiyama, Takuro Sunada, Takayuki Goto, Takashi Kobayashi, Hitoshi Yamada, Norihiko Tsuchiya, Tomomi Kamba, Hideyasu Matsuyama, Tomonori Habuchi, Masatoshi Eto, Chikara Ohyama, Akihiro Ito, Hiroyuki Nishiyama, Hiroshi Okuno, Toshiyuki Kamoto, Akihiro Fujimoto, Osamu Ogawa, Shusuke Akamatsu
Summary: Detecting low-frequency ctDNA variants with a VAF <1% is important for identifying clinically informative genomic alterations in CRPC. Significant differences in PFS and OS were found when applying a ctDNA fraction cutoff value of 0.4%, particularly in patients with defects in ATM, BRCA2, and TP53.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Emma St Martin, Alejandro Ferrer, Abhishek A. Mangaonkar, Shakila P. Khan, Mira A. Kohorst, Avni Y. Joshi, William J. Hogan, Horatiu Olteanu, Ann M. Moyer, Aref Al-Kali, Ayalew Tefferi, Dong Chen, Kitsada Wudhikarn, Ronald Go, David Viswanatha, Rong He, Rhett Ketterling, Phuong L. Nguyen, Jennifer L. Oliveira, Naseema Gangat, Terra Lasho, Mrinal M. Patnaik
Summary: Germline predisposition syndromes (GPS) are caused by constitutional abnormalities in tumor suppressive and homeostatic genes, leading to an increased risk of neoplasia in affected individuals. This study presented clinical and genomic data on 144 Mayo Clinic patients with GPS, revealing distinct patterns in different subtypes of GPS and the importance of comprehensive management approaches for patients with hematological neoplasms.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Biochemical Research Methods
Zhenxing Guo, Andrew M. Shafik, Peng Jin, Zhijin Wu, Hao Wu
Summary: In this work, a novel statistical method is developed to identify mRNA epigenetic modification regions from MeRIP-seq data, based on an empirical Bayesian hierarchical model. This method accounts for various sources of variations in the data through rigorous modeling and applies shrinkage estimation by borrowing information from transcriptome-wide data to stabilize the parameter estimation, showing higher accuracy, robustness, and efficiency compared to existing peak calling methods in simulation and real data analyses.