Article
Oncology
Majd Jawad, Michelle Afkhami, Yi Ding, Xiaohui Zhang, Peng Li, Kim Young, Mina Luqing Xu, Wei Cui, Yiqing Zhao, Stephanie Halene, Aref Al-Kali, David Viswanatha, Dong Chen, Rong He, Gang Zheng
Summary: DNMT3A R882 mutations in myelodysplastic syndrome (MDS) are associated with more severe symptoms, worse prognosis, and an increased risk of progression to acute myeloid leukemia (AML). Non-R882 mutations do not show these associations. Coexisting SF3B1 or SRSF2 mutations mitigate the higher risk of AML transformation and worse progression-free survival (PFS) in DNMT3A R882 mutant MDS cases.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Laneshia K. Tague, Karolyn A. Oetjen, Anirudh Mahadev, Matthew J. Walter, Hephzibah Anthony, Daniel Kreisel, Daniel C. Link, Andrew E. Gelman
Summary: Clonal hematopoiesis (CH) in DNA damage response (DDR) genes is prevalent in lung transplant recipients and is associated with posttransplant outcomes including cytomegalovirus activation and mycophenolate intolerance.
Article
Oncology
Tanja Bozic, Chao-Chung Kuo, Jan Hapala, Julia Franzen, Monika Eipel, Uwe Platzbecker, Martin Kirschner, Fabian Beier, Edgar Jost, Christian Thiede, Wolfgang Wagner
Summary: The study proposed an alternative method to estimate MRD based on AML-associated DNA methylation patterns, which could reliably distinguish malignant and healthy samples by identifying abnormal DNAm patterns. However, since healthy samples may also contain abnormal-classified DNAm reads, the approach does not yet reliably differentiate between MRD positive and negative samples.
Editorial Material
Hematology
John S. Welch
Summary: This study integrated mutational analysis with clinical outcomes and proposed merging TP53-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and TP53-mutated acute myeloid leukemia (AML) into a unified diagnosis. The researchers found no significant difference between these two diseases in terms of clinical parameters and survival outcomes.
Article
Biochemistry & Molecular Biology
Dominik Kodada, Michaela Hyblova, Patrik Krumpolec, Nikola Janostiakova, Peter Barath, Marian Grendar, Gabriela Blandova, Oliver Petrovic, Pavol Janega, Vanda Repiska, Gabriel Minarik
Summary: Endometrial cancer is a common gynecologic cancer type with increasing incidence globally. Molecular classification has shown promise in providing accurate prognostic factors and personalized treatment, while diagnostic methods lag behind. Minimally invasive liquid biopsies could be an alternative screening and diagnostic approach.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Tianpeng Gu, Dapeng Hao, Junsung Woo, Teng-Wei Huang, Lei Guo, Xueqiu Lin, Anna G. Guzman, Ayala Tovy, Carina Rosas, Mira Jeong, Yubin Zhou, Benjamin Deneen, Yun Huang, Wei Li, Margaret A. Goodell
Summary: This study reveals the essential role of the long isoform (DNMT3A1) of DNA methyltransferase 3a (DNMT3A) in mouse postnatal development. DNMT3A1 specifically regulates bivalent neurodevelopmental genes in the brain. The N terminus of DNMT3A1 is shown to be necessary for normal development and DNA methylation at DNMT3A1-enriched regions, possibly through binding to mono-ubiquitinated histone H2AK119. These findings provide insights into the isoform-specific functions and regulatory mechanisms of DNMT3A in development.
Article
Cell & Tissue Engineering
Daniel Hormaechea-Agulla, Katie A. Matatall, Duy T. Le, Bailee Kain, Xiaochen Long, Pawel Kus, Roman Jaksik, Grant A. Challen, Marek Kimmel, Katherine Y. King
Summary: The study demonstrates that IFN gamma signaling induced during chronic infection can drive DNMT3A-loss-of-function clonal hematopoiesis. This suggests that environmental factors play an important role in the development of CH.
Article
Hematology
Isabelle A. van Zeventer, Jonas B. Salzbrunn, Aniek O. de Graaf, Bert A. van der Reijden, H. Marike Boezen, Judith M. Vonk, Pim van der Harst, Jan Jacob Schuringa, Joop H. Jansen, Gerwin Huls
Summary: In individuals aged 80 years or older, the presence of clonal hematopoiesis (CH) is not associated with a higher risk of death as observed in this study. Mutations in DNMT3A and TET2 genes are common in this age group, and the presence of mutations in genes other than DNMT3A or TET2 may increase the risk of death. Further research is needed to understand the mechanisms underlying these associations.
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)
Article
Multidisciplinary Sciences
Seiichi Yano, Takashi Ishiuchi, Shusaku Abe, Satoshi H. Namekawa, Gang Huang, Yoshihiro Ogawa, Hiroyuki Sasaki
Summary: DNMT3A is guided by both H3K36me2 and H3K36me3 to methylate DNA in mouse oocytes, with these two histone marks comprising the minimal chromatin signature for global DNA methylation. Depletion of H3K36me2 affects DNA methylation in moderately methylated regions and alters the methylation pattern of the X chromosome. Simultaneous depletion of H3K36me2 and H3K36me3 results in global hypomethylation, similar to DNMT3A depletion.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jianan Zheng, Zhongwang Wang, Xiangyu Pan, Zhixin Zhang, He Li, Xintong Deng, Pengpeng Liu, Qi Zhang, Feifei Na, Chong Chen, Ting Niu, Yu Liu
Summary: This study found that mutations in the DNMT3A gene accelerate the development of angioimmunoblastic T-cell lymphoma (AITL) and lead to the expansion of malignant Tfh cells and aberrant B cells, resulting in shortened disease-free survival.
Article
Multidisciplinary Sciences
Gabor Bedics, Peter Szoke, Bence Batai, Tibor Nagy, Gergo Papp, Noemi Kranitz, Hajnalka Rajnai, Lilla Reiniger, Csaba Bodor, Balint Scheich
Summary: In this study, comprehensive genomic analysis was performed on ATRX-deficient IDH-wildtype adult high-grade gliomas, revealing mutually exclusive mutations in ATRX and pTERT. The genetic characteristics of these tumors suggest potential therapeutic interventions including immunotherapies combined with MAPK pathway inhibition and DNA repair inhibitors.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Christopher M. Arends, Thomas G. Liman, Paulina M. Strzelecka, Anna Kufner, Pelle Loewe, Shufan Huo, Catarina M. Stein, Sophie K. Piper, Marlon Tilgner, Pia S. Sperber, Savvina Dimitriou, Peter U. Heuschmann, Raphael Hablesreiter, Christoph Harms, Lars Bullinger, Joachim E. Weber, Matthias Endres, Frederik Damm
Summary: Clonal hematopoiesis (CH) is common among older people and is associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. This study investigated CH in patients with first-ever ischemic stroke and found that CH is associated with an increased risk of recurrent vascular events and death.
Article
Multidisciplinary Sciences
Aristeidis G. Telonis, Qin Yang, Hsuan-Ting Huang, Maria E. Figueroa
Summary: DNMT3A and IDH1/2 mutations together regulate the transcriptome and the epigenome in acute myeloid leukemia. The study found that genes with significant expression-methylation correlations are enriched in signaling and metabolic pathways. The common feature of these methylation-regulated genes is the density of MIR retrotransposons in their introns.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Xian Chen, Chuchu Tian, Zhuanghui Hao, Lingang Pan, Minglin Hong, Wei Wei, Daniel Muteb Muyey, Hongwei Wang, Xiuhua Chen
Summary: In this study, we investigated the biological and prognostic significance of DNMT3A mutations in acute myeloid leukemia (AML) by analyzing 171 adult patients with de novo cytogenetically normal AML. DNMT3A(High) patients with a variant allele frequency (VAF) above 42% showed higher white blood cell count, higher lactate dehydrogenase level, lower complete remission rate, and shorter overall survival compared to DNMT3A(Low) patients. We also identified two different comutated genotypes, DNMT3A(mut)NPM1(mut)FLT3-ITDmut and DNMT3A(mut)IDH1/IDH2(mut), which showed different clinical outcomes. Multivariate analyses revealed that DNMT3A(High) and DNMT3A(mut)NPM1(mut)FLT3-ITDmut were independently associated with lower complete remission rate and shorter overall survival and relapse-free survival, respectively.
Article
Hematology
Christopher Maximilian Arends, Savvina Dimitriou, Arndt Stahler, Raphael Hablesreiter, Paulina M. Strzelecka, Catarina M. Stein, Marlon Tilgner, Ryunosuke Saiki, Seishi Ogawa, Lars Bullinger, Dominik P. Modest, Sebastian Stintzing, Volker Heinemann, Frederik Damm
Article
Cardiac & Cardiovascular Systems
Maren Schmiester, Eva Tranter, Alessandro Lorusso, Florian Blaschke, Dominik Geisel, Lars Bullinger, Frederik Damm, Il-Kang Na
Summary: Burkitt lymphoma is a rare disease with abdominal involvement, but cardiac involvement is extremely rare. This case report describes a patient with cardiac involvement in Burkitt lymphoma, who experienced transient deterioration of cardiac function after chemotherapy but eventually achieved full recovery.
BMC CARDIOVASCULAR DISORDERS
(2022)
Article
Chemistry, Medicinal
Sahil Arora, Gaurav Joshi, Anuhar Chaturvedi, Michael Heuser, Santoshkumar Patil, Raj Kumar
Summary: The allosteric regulation of pyruvate kinase M2 (PKM2) plays a significant role in cellular activity and has potential applications in treating metabolic dysfunction and related conditions. This perspective article focuses on medicinal chemistry strategies for designing PKM2 inhibitors and activators with improved efficacy and selectivity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Friederike Christen, Raphael Hablesreiter, Kaja Hoyer, Cornelius Hennch, Antje Maluck-Boettcher, Angela Segler, Annett Madadi, Mareike Frick, Lars Bullinger, Franziska Briest, Frederik Damm
Summary: By using CRISPR/Cas9 technology to introduce mutations in healthy, young hematopoietic progenitor cells from umbilical cord blood samples, this study investigated the impact of clonal hematopoiesis-associated gene mutations on human stem and progenitor cells. The results showed enhanced self-renewal capacities in TET2 mutated cells and a mutation-specific impact on clonal composition of HSPCs after long-term culture experiments. This study provides evidence for the direct impact of clonal hematopoiesis-associated mutations on self-renewal and clonal composition of human stem and progenitor cells without confounding factors like age or a complex mutational landscape.
Letter
Hematology
Jasper David Feldkamp, Valentin Max Vetter, Christopher Maximilian Arends, Tonio Johannes Lukas Lang, Lars Bullinger, Frederik Damm, Ilja Demuth, Mareike Frick
Article
Oncology
Yasuhide Takeuchi, Kenichi Yoshida, Adriane Halik, Annegret Kunitz, Hiromichi Suzuki, Nobuyuki Kakiuchi, Yusuke Shiozawa, Akira Yokoyama, Yoshikage Inoue, Tomonori Hirano, Tetsuichi Yoshizato, Kosuke Aoki, Yoichi Fujii, Yasuhito Nannya, Hideki Makishima, Berit Maria Pfitzner, Lars Bullinger, Masahiro Hirata, Keita Jinnouchi, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Takeshi Okamoto, Hironori Haga, Seishi Ogawa, Frederik Damm
Summary: Myxofibrosarcoma (MFS) is a rare subtype of sarcoma with complex genetic basis. This study analyzed 69 MFS cases and identified various genetic abnormalities, including mutations and copy number alterations in known disease drivers, as well as previously unknown gene aberrations. Longitudinal analysis revealed an increase in mutation number and significant changes in clonal composition over time.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Oncology
Adriane Halik, Christopher Maximilian Arends, Lars Bullinger, Frederik Damm, Mareike Frick
Summary: Acute myeloid leukemia (AML) is an aggressive cancer characterized by DNA mutations. These mutations can predict the response to treatment and may change during therapy. Since 2017, there has been a significant increase in treatment options for AML, and genetic profiling has played a crucial role in clinical studies.
Article
Biochemistry & Molecular Biology
Jessica Schneider, Leonie Kuhlmann, Yankai Xiao, Solaiman Raha, Gunter Bernhardt, Michael Stadler, Felicitas Thol, Michael Heuser, Matthias Eder, Arnold Ganser, Sarina Ravens, Reinhold Forster, Immo Prinz, Christian Koenecke, Christian R. Schultze-Florey
Summary: Donor lymphocyte infusion (DLI) can induce durable remission in relapsing patients after alloHSCT, but it carries the risk of graft-versus-host disease (GVHD). This study analyzed T cells in patients receiving DLI after alloHSCT and found that GVHD was associated with changes in the T-cell receptor (TCR) repertoire. The dynamics of CD4(+)CD25(+)CD127(low) regulatory T cells (T-reg cells) and CD4(+) conventional T cells (T-con cells) TCR repertoire could be helpful in diagnosing and monitoring GVHD following DLI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Fengbiao Zhou, Nesrine Aroua, Yi Liu, Christian Rohde, Jingdong Cheng, Anna-Katharina Wirth, Daria Fijalkowska, Stefanie Goellner, Michelle Lotze, Haiyang Yun, Xiaobing Yu, Caroline Pabst, Tim Sauer, Thomas Oellerich, Hubert Serve, Christoph Roellig, Martin Bornhaeuser, Christian Thiede, Claudia Baldus, Michaela Frye, Simon Raffel, Jeroen Krijgsveld, Irmela Jeremias, Roland Beckmann, Andreas Trumpp, Carsten Mueller-Tidow
Summary: The dynamic 2'-O-methylation of ribosomal RNA regulates leukemia stem cell activity in acute myeloid leukemia. The methylation pattern is associated with AML development stage and stem cell gene expression. Enhanced 2'-O-methylation redirects ribosome translation and controls AML stem cell self-renewal.
Article
Hematology
Christopher M. Arends, Thomas G. Liman, Paulina M. Strzelecka, Anna Kufner, Pelle Loewe, Shufan Huo, Catarina M. Stein, Sophie K. Piper, Marlon Tilgner, Pia S. Sperber, Savvina Dimitriou, Peter U. Heuschmann, Raphael Hablesreiter, Christoph Harms, Lars Bullinger, Joachim E. Weber, Matthias Endres, Frederik Damm
Summary: Clonal hematopoiesis (CH) is common among older people and is associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. This study investigated CH in patients with first-ever ischemic stroke and found that CH is associated with an increased risk of recurrent vascular events and death.
Meeting Abstract
Oncology
June Takeda, Kenichi Yoshida, Masahiro M. Nakagawa, Yasuhito Nannya, Akinori Yoda, Ryunosuke Saiki, Yotaro Ochi, Lanying Zhao, Rurika Okuda, Xingxing Qi, Takuto Mori, Ayana Kon, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Ming-Chung Kuo, Cassandra Kerr, Yasunobu Nagata, Daisuke Morishita, Nobuhiro Hiramoto, Akira Hangaishi, Hideyuki Nakazawa, Ken Ishiyama, Satoru Miyano, Shigeru Chiba, Yasushi Miyazaki, Toshiyuki Kitano, Kensuke Usuki, Nobuo Sezaki, Hisashi Tsurumi, Shuichi Miyawaki, Jaroslaw P. Maciejewski, Takayuki Ishikawa, Kazuma Ohyashiki, Arnold Ganser, Michael Heuser, Felicitas Thol, Lee-Yung Shih, Akifumi Takaori-Kondo, Hideki Makishima, Seishi Ogawa
Meeting Abstract
Biophysics
C. Craddock, U. Platzbecker, M. Heuser, V. Pullarkat, S. Chaudhury, D. Wu, S. Addo, B. Chyla, Q. Jiang, P. Lee, J. E. Wolff
BONE MARROW TRANSPLANTATION
(2022)
Article
Medicine, General & Internal
Christopher Maximilian Arends, Frederik Damm
Summary: The prevalence of clonal hematopoiesis (CH) in patients with solid neoplasms is significant. CH, particularly mutations in DNA damage repair genes, is associated with a higher risk of therapy-associated myeloid neoplasms (t-MN). Understanding the role of CH in this patient population and developing evidence-based recommendations for action are crucial.
Article
Oncology
June Takeda, Kenichi Yoshida, Masahiro M. Nakagawa, Yasuhito Nannya, Akinori Yoda, Ryunosuke Saiki, Yotaro Ochi, Lanying Zhao, Rurika Okuda, Xingxing Qi, Takuto Mori, Ayana Kon, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Ming-Chung Kuo, Cassandra M. Kerr, Yasunobu Nagata, Daisuke Morishita, Nobuhiro Hiramoto, Akira Hangaishi, Hideyuki Nakazawa, Ken Ishiyama, Satoru Miyano, Shigeru Chiba, Yasushi Miyazaki, Toshiyuki Kitano, Kensuke Usuki, Nobuo Sezaki, Hisashi Tsurumi, Shuichi Miyawaki, Jaroslaw P. Maciejewski, Takayuki Ishikawa, Kazuma Ohyashiki, Arnold Ganser, Michael Heuser, Felicitas Thol, Lee-Yung Shih, Akifumi Takaori-Kondo, Hideki Makishima, Seishi Ogawa
Summary: This study reveals the significant role of gains, amplifications, and mutations of EPOR and JAK2 in the pathogenesis of pure erythroleukemia. The frequent response of these cases to ruxolitinib highlights the potential therapeutic role of JAK2 inhibition for erythroleukemia with EPOR/JAK2-involving lesions.
BLOOD CANCER DISCOVERY
(2022)
Meeting Abstract
Transplantation
Nicole Brueder, Jan T. Kielstein, Luca-Marie Heinze, Catherina Lueck, Victoria Panagiota, Elke Dammann, Sophia Koehler, Steven Talbot, Michael Stadler, Michael Heuser, Arnold Ganser, Matthias Eder, Gernot Beutel
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
