Review
Hematology
Hsuan-Ting Huang, Maria E. Figueroa
Summary: Epigenetic deregulation is a recognized mechanism in the development of myeloid malignancies, with studies showing patterns of aberrant DNA methylation, altered chromatin states, and mutations in chromatin modifiers. Understanding these disease mechanisms can lead to new therapeutic interventions, especially in the context of existing chemotherapy standards.
Review
Biochemistry & Molecular Biology
Deirdra Venney, Adone Mohd-Sarip, Ken Mills
Summary: Myeloid malignancy encompasses a range of diseases including MPN, MDS, and AML, with genomic studies revealing numerous somatic mutations and highlighting the importance of epigenetic mutations in disease progression. Key genes like DNMT3A, TET2, ASXL1, EZH2, and IDH1/2 play critical roles in disease pathogenesis. Advances in understanding disease progression, mutational profiles, and therapeutic potential are continually improving our knowledge of myeloid malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Inkyung Jung, Jungeun An, Myunggon Ko
Summary: Epigenetic modifications play crucial roles in gene expression regulation and are commonly dysregulated in cancers, influencing cell lineage differentiation, survival, and proliferation. Aberrant epigenetic modifications confer unique characteristics to tumor cells, leading to sustained proliferation, resistance to growth-suppressive or cell death signals, replicative immortality, invasion, and metastasis. DNA cytosine methylation-demethylation, among various epigenetic mechanisms in mammals, is frequently disrupted in cancers. Targeting DNA methylation dynamics has gained attention as a promising therapeutic approach to restore normal conditions affected by cancer-specific epigenetic abnormalities. Small molecules targeting DNA (de)methylation regulators have been developed as potential cancer therapeutics, with some already approved for clinical usage and many others undergoing clinical trials.
Review
Medicine, General & Internal
Iosif Papafragkos, Efrosyni Markaki, Christina Kalpadakis, Panayotis Verginis
Summary: Myeloid-derived suppressor cells (MDSCs) are potent regulators of the immune system, playing a role in cancer but their specific contribution to lymphomas remains unclear. This review focuses on MDSCs in lymphomas, discussing literature and lessons learned from animal models, and highlights future research directions and challenges in understanding the immune system complexities in malignancies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Ricardo D. Parrondo, Madiha Iqbal, Reinhard Von Roemeling, Christina Von Roemeling, Han W. Tun
Summary: Mutations in MYD88L265P gene play a key role in several B-cell lymphomas, and IRAK-4 inhibitors show therapeutic potential in B-cell lymphomas and certain myeloid malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Christine Birdwell, Warren Fiskus, Tapan M. Kadia, Courtney D. DiNardo, Christopher P. Mill, Kapil N. Bhalla
Summary: EVI1 is an oncogenic zinc-finger transcription factor that is overexpressed in myeloid malignancies and correlates with poor clinical outcomes. Despite advancements in understanding the biology of EVI1 dysregulation, significant improvements in therapeutic outcomes remain elusive.
BLOOD CANCER JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hannah Petraitis Kuschman, Marianne B. Palczewski, Douglas D. Thomas
Summary: Nitric oxide (NO) and hydrogen sulfide (H2S) are now recognized as potent gaseous messenger molecules that rapidly transduce cellular signals and regulate various physiological functions. They often work synergistically and competitively to modulate each other's activity through chemical reactions and modifications to protein targets. In addition to their canonical modes of action, increasing evidence has shown that they also share the signaling mechanism of epigenetic regulation.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Review
Oncology
Shifen Wang, Xingyun Zhao, Siwen Wu, Dawei Cui, Zhenshu Xu
Summary: In this review, the biological functions, phenotypic characteristics, suppressive mechanisms, and expansion of MDSC populations in various types of hematological malignancies are summarized. The clinical correlation between MDSCs and the diagnosis of malignant hematological diseases, as well as the drugs targeting MDSCs, are discussed. Furthermore, the therapeutic strategies combining MDSCs targeting with other immunotherapies, such as immune checkpoint inhibitors, are highlighted.
BIOMARKER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Kah Poh Loh, Chandrika Sanapala, Marielle Jensen-Battaglia, Anish Rana, Michael B. Sohn, Erin Watson, Nikesha Gilmore, Heidi D. Klepin, Jason H. Mendler, Jane Liesveld, Eric Huselton, Marissa LoCastro, Martha Susiarjo, Colleen Netherby-Winslow, AnnaLynn M. Williams, Karen Mustian, Paula Vertino, Michelle C. Janelsins
Summary: This study aimed to investigate the associations between accelerated DNAm age and physical, psychological, and cognitive functions in older adults with myeloid malignancies, as well as the effects of exercise intervention on DNAm age and functional outcomes. The results showed that exercise intervention can reduce accelerated DNAm age and improve physical performance.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Editorial Material
Oncology
Haydn Kissick, Rafi Ahmed
Summary: In this article, Belk et al. conducted an in vitro CRISPR screen to identify genes that regulate CD8(+) T cell exhaustion. They discovered several genes related to epigenetic modification and demonstrated that eliminating Arid1a enables CD8(+) T cells to retain their proliferative and cytotoxic function in vivo, resulting in improved anti-tumor activity.
Review
Genetics & Heredity
Cecilia Pessoa Rodrigues, Maria Shvedunova, Asifa Akhtar
Summary: Hematopoiesis is the process of deriving all blood cells from a single multipotent progenitor cell, hematopoietic stem cells, in both fetal and adult organisms. The correct execution of this process relies on the interaction between genetically encoded differentiation programs and various cell-intrinsic and cell-extrinsic factors. Recent studies have highlighted the significant contributions of epigenetic modifiers to HSC self-renewal and lineage specification.
TRENDS IN GENETICS
(2021)
Article
Hematology
D. Thomalla, L. Beckmann, C. Grimm, M. Oliverio, L. Meder, C. D. Herling, P. Nieper, T. Feldmann, O. Merkel, E. Lorsy, A. da Palma Guerreiro, J. von Jan, I. Kisis, E. Wasserburger, J. Claasen, E. Faitschuk-Meyer, J. Altmueller, P. Nuernberg, T. -P. Yang, M. Lienhard, R. Herwig, K. -A. Kreuzer, C. P. Pallasch, R. Buettner, S. C. Schaefer, J. Hartley, H. Abken, M. Peifer, H. Kashkar, G. Knittel, B. Eichhorst, R. T. Ullrich, M. Herling, H. C. Reinhardt, M. Hallek, M. R. Schweiger, L. P. Frenzel
Summary: This study explores the role of epigenetic events in venetoclax resistance in aggressive lymphoma and high-risk CLL patients. It identifies methylation of a regulatory CpG island within the PUMA promoter as a mechanism for mediating PUMA downregulation and resistance to venetoclax. The loss of PUMA results in metabolic reprogramming and higher oxidative phosphorylation, resembling the metabolic phenotype associated with venetoclax resistance. Additionally, it highlights the critical role of BAX-mediated apoptosis in drug resistance and provides potential therapeutic targets to overcome venetoclax resistance.
Article
Biochemistry & Molecular Biology
Abhishek Niroula, Aswin Sekar, Mark A. Murakami, Mark Trinder, Mridul Agrawal, Waihay J. Wong, Alexander G. Bick, Md Mesbah Uddin, Christopher J. Gibson, Gabriel K. Griffin, Michael C. Honigberg, Seyedeh M. Zekavat, Kaavya Paruchuri, Pradeep Natarajan, Benjamin L. Ebert
Summary: Studies have shown that clonal hematopoiesis and mosaic chromosomal alterations are associated with lineage-specific hematologic malignancies, and these genetic alterations can be used in combination with blood count parameters to identify individuals at high risk.
Review
Biochemistry & Molecular Biology
Nieves Lara-Urena, Vahid Jafari, Mario Garcia-Dominguez
Summary: SUMOylation is an important post-translational modification that regulates diverse physiological processes. Dysregulation of the SUMO pathway, involving proteases and ligases, is associated with cancer initiation and progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Yixuan Zhang, Mingrui Li, Yiming Guo, Shuang Liu, Yongguang Tao
Summary: Ferroptosis differs significantly from other types of cell death in biochemical processes, morphological changes, and genetics as a unique programmed cell death. In this paper, we summarize the current literature on ferroptosis, including the cascade reaction of key material metabolism, organelle dysfunction, the relationship between different organelles, and the impact of positive and negative key regulatory factors on ferroptosis at the epigenetic level. Based on material metabolism or epigenetic regulation, it is evident that the regulatory network of ferroptosis is interrelated and complex.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biology
Chan-Wang J. Lio, Xiaojing Yue, Isaac F. Lopez-Moyado, Mamta Tahiliani, L. Aravind, Anjana Rao
JOURNAL OF BIOSCIENCES
(2020)
Review
Immunology
Chan-Wang Jerry Lio, Stanley Ching-Cheng Huang
Article
Immunology
Mariko Takahashi, Chan-Wang J. Lio, Anaamika Campeau, Martin Steger, Ferhat Ay, Matthias Mann, David J. Gonzalez, Mohit Jain, Sonia Sharma
Summary: In this study, Sharma and colleagues identified DAPK3 as a positive regulator of the STING-interferon-beta activation pathway, essential for driving tumor-intrinsic innate immunity and tumor immune surveillance. Loss of DAPK3 expression or kinase activity impaired STING activation, reduced infiltration of immune cells, and attenuated the response to cancer chemo-immunotherapy. DAPK3 coordinates post-translational modification of STING and is critical for maintaining STING activation and immune response against tumors.
Article
Biochemistry & Molecular Biology
Xiaojing Yue, Daniela Samaniego-Castruita, Edahi Gonzalez-Avalos, Xiang Li, Benjamin G. Barwick, Anjana Rao
Summary: TET proteins are essential for maintaining the molecular features of Treg cells and promoting their dependence on IL-2, while vitamin C can enhance Treg signature gene expression and alter the epigenetic landscape.
Article
Immunology
Hyungseok Seo, Edahi Gonzalez-Avalos, Wade Zhang, Payal Ramchandani, Chao Yang, Chan-Wang J. Lio, Anjana Rao, Patrick G. Hogan
Summary: BATF and IRF4 cooperate to counter T cell exhaustion in mouse tumor models, promoting better tumor control by CAR T cells.
Review
Immunology
Ankita Saini, Hazem E. Ghoneim, Chan-Wang Jerry Lio, Patrick L. Collins, Eugene M. Oltz
Summary: Cell identity and function are determined by the programming of transcriptomes, which is regulated by transcription factors and enhancers. In immune cells, this regulation is especially complex and flexible, allowing for cell-specific gene expression in response to different signals.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Review
Immunology
Heng-Yi Chen, Michael Hsu, Chan-Wang Jerry Lio
Summary: Micronutrients are essential for survival and their deficiency can lead to weakened immune responses. Recent studies suggest that micronutrients may regulate adaptive immune responses by influencing epigenetic remodeling.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Vipul Shukla, Daniela Samaniego-Castruita, Zhen Dong, Edahi Gonzalez-Avalos, Qingqing Yan, Kavitha Sarma, Anjana Rao
Summary: Loss of TET methylcytosine dioxygenases in B cells is associated with increased DNA-RNA hybrids and G-quadruplex DNA structures, leading to genomic instability and the development of germinal center-derived lymphomas. Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated depletion of nucleases and helicases that regulate G-quadruplexes and R-loops reduces the viability of TET-deficient B cells.
Article
Biology
Elitsa Stoyanova, Michael Riad, Anjana Rao, Nathaniel Heintz
Summary: At birth, the mammalian brain contains billions of neurons, which develop into networks and learn adult brain tasks through chemical marks such as methylation and hydroxymethylation. Accumulation of 5hmC, possibly essential for neuronal maturation, highlights the role of Tet proteins in preparing and removing DNA marks. Problematic control of 5hmC levels could potentially contribute to brain disorders, while future studies may provide insights into cancerous cell development due to loss of 5hmC.
Article
Cell Biology
Lizhen Wu, Vipul Shukla, Anurupa Devi Yadavalli, Ravi K. Dinesh, Dijin Xu, Anjana Rao, David G. Schatz
Summary: The DNA repair factor HMCES can strongly suppress deletions, facilitating the production of antigen-specific antibodies. Their findings propose a novel model for protecting Ig gene integrity during SHM.
GENES & DEVELOPMENT
(2022)
Article
Immunology
Lydia N. Raines, Haoxin Zhao, Yuzhu Wang, Heng-Yi Chen, Hector Gallart-Ayala, Pei-Chun Hsueh, Wei Cao, Yeojung Koh, Ana Alamonte-Loya, Pu-Ste Liu, Julijana Ivanisevic, Chan-Wang Jerry Lio, Ping-Chih Ho, Stanley Ching-Cheng Huang
Summary: This study reveals the importance of PERK signaling and PSAT1-mediated serine metabolism in promoting the immunosuppressive function of M2 macrophages, providing new insights into the molecular mechanisms of immune cell suppressive phenotype.
Article
Biology
Heng-Yi Chen, Ana Almonte-Loya, Fang-Yun Lay, Michael Hsu, Eric Johnson, Edahi Gonzalez-Avalos, Jieyun Yin, Richard S. Bruno, Qin Ma, Hazem E. Ghoneim, Daniel J. Wozniak, Fiona E. Harrison, Chan-Wang Jerry Lio
Summary: Vitamin C is an essential micronutrient that enhances antibody response by promoting plasma cell differentiation through IL-21/STAT3 signaling pathway. As a cofactor for epigenetic enzymes, it facilitates DNA modification and demethylation, thereby influencing gene expression and cell fate decisions in the immune system.
Article
Oncology
Brian M. Reilly, Timothy Luger, Soo Park, Chan-Wang Jerry Lio, Edahi Gonzalez-Avalos, Emily C. Wheeler, Minjung Lee, Laura Williamson, Tiffany Tanaka, Dinh Diep, Kun Zhang, Yun Huang, Anjana Rao, Rafael Bejar
Summary: Mutations in the DNA methylation regulating gene TET2 are associated with response to DNA methyltransferase inhibitors, but the exact mechanisms are still unknown. TET2 loss influences DNA methylation and hydroxymethylation patterns at erythroid gene enhancers during 5-Aza treatment, leading to downregulation of erythroid gene expression. Treatment with 5-Aza disproportionately induces expression of down-regulated genes in TET2KO cells, with dynamic 5mC changes at erythroid gene enhancers playing a key role.
MOLECULAR CANCER RESEARCH
(2021)
Article
Immunology
Anjana Rao