Article
Oncology
Jennifer M. SanMiguel, Elizabeth Eudy, Matthew A. Loberg, Kira A. Young, Jayna J. Mistry, Kristina D. Mujica, Logan S. Schwartz, Timothy M. Stearns, Grant A. Challen, Jennifer J. Trowbridge
Summary: Clonal hematopoiesis resulting from enhanced fitness of mutant hematopoietic stem cells can lead to both favorable and unfavorable health outcomes. This study found that aging-induced TNF alpha signaling promotes the selective advantage of mutant HSCs and stimulates the production of mutant B lymphoid cells. The loss of TNFR1 abolishes the advantage of mutant HSCs, while the loss of TNFR2 results in overproduction of mutant myeloid cells without affecting HSC fitness.
Article
Biochemistry & Molecular Biology
Petra Buettner, Julia Boettner, Knut Krohn, Ronny Baber, Uwe Platzbecker, Michael Cross, Steffen Desch, Holger Thiele, Sabine Steiner, Dierk Scheinert, Klaus H. Metzeler, Daniela Branzan
Summary: In this pilot study, it was found that clonal hematopoiesis (CH)-associated mutations can be detected in both peripheral blood cells and tissues associated with atherosclerosis, suggesting a potential impact on disease physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Mridul Agrawal, Abhishek Niroula, Pierre Cunin, Marie McConkey, Veronica Shkolnik, Peter G. Kim, Waihay J. Wong, Lachelle D. Weeks, Amy E. Lin, Peter G. Miller, Christopher J. Gibson, Aswin Sekar, Inga-Marie Schaefer, Donna Neuberg, Richard M. Stone, Alexander G. Bick, Md Mesbah Uddin, Gabriel K. Griffin, Siddhartha Jaiswal, Pradeep Natarajan, Peter A. Nigrovic, Deepak A. Rao, Benjamin L. Ebert
Summary: Gout is a common inflammatory arthritis caused by hyperuricemia. This study found that CHIP, a condition related to hematologic cancers and cardiovascular disease, is associated with an increased risk of gout. Additionally, MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models.
Review
Cardiac & Cardiovascular Systems
Anna Stein, Klaus Metzeler, Anne Sophie Kubasch, Karl-Philipp Rommel, Steffen Desch, Petra Buettner, Maciej Rosolowski, Michael Cross, Uwe Platzbecker, Holger Thiele
Summary: Cardiovascular and oncological diseases are the leading causes of death globally. Clonal hematopoiesis (CH), defined as clonal expansion of peripheral blood cells without hematological malignancy, has been identified as a novel and far-reaching risk factor for both diseases. CH increases the risk of cardiovascular events, malignant transformation, and all-cause mortality. It is associated with worse outcomes in arteriosclerotic events and heart failure. Chronic inflammation and clonal expansion are suggested to be the major functional link. Further research is needed to fully understand and clinically manage CH.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Min Liao, Ruiqing Chen, Yang Yang, Hanqing He, Liqian Xu, Yuxuan Jiang, Zhenxing Guo, Wei He, Hong Jiang, Jianwei Wang
Summary: Aging-related DNMT3A R882H-driven clonal hematopoiesis is a risk factor for myeloid malignancies remission and overall survival. The study found that DNMT3A R878H bone marrow cells exhibit enhanced reconstitution capacity in aged bone marrow environment and protection against inflammatory insults. Mechanistically, R878H cells showed compromised necroptosis signaling in response to proliferation stress and TNF alpha insults, providing insights into the molecular mechanism driving clonal hematopoiesis.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Neurosciences
Woo-Jin Lee, Keun-Hwa Jung, Han Song, Heesun Lee, Hyo Eun Park, Youngil Koh, Su-Yeon Choi, Kyung-Il Park
Summary: This study investigated the association between clonal hematopoiesis of indeterminate potential (CHIP) and cerebral white matter hyperintensity (WMH). The results showed that clonal hematopoiesis with DNMT3A mutation was quantitatively associated with a lower volume of cerebral WMH. This suggests that CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Yongliang Zhang, Yu Yao, Yaping Xu, Lifeng Li, Yan Gong, Kai Zhang, Meng Zhang, Yanfang Guan, Lianpeng Chang, Xuefeng Xia, Lin Li, Shuqin Jia, Qiang Zeng
Summary: The study conducted a ctDNA-based analysis on over 10,000 pan-cancer Chinese patients, revealing age-related CH variants, detection rates of ctDNA in different cancer types, and the frequencies of potential driver genes. The findings may be valuable for identifying therapeutic targets and developing combined treatment strategies.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Shengfang Wang, Sining Hu, Xing Luo, Xiaoyi Bao, Ji Li, Minghao Liu, Ying Lv, Chen Zhao, Ming Zeng, Xi Chen, Amanda Unsworth, Sarah Jones, Thomas W. Johnson, Stephen J. White, Haibo Jia, Bo Yu
Summary: This study investigated the prevalence of mutations in DNMT3A and TET2 in STEMI patients and their association with prognosis. The study found that over 10% of STEMI patients carried DNMT3A or TET2 mutations, which were significantly associated with poorer prognosis, possibly due to higher levels of inflammatory cytokines in mutation carriers.
Article
Oncology
Cosimo Cumbo, Francesco Tarantini, Antonella Zagaria, Luisa Anelli, Crescenzio Francesco Minervini, Nicoletta Coccaro, Giuseppina Tota, Luciana Impera, Elisa Parciante, Maria Rosa Conserva, Immacolata Redavid, Paola Carluccio, Mario Delia, Annamaria Giordano, Maria Chiara Longo, Tommasina Perrone, Antonella Russo Rossi, Giorgina Specchia, Pellegrino Musto, Francesco Albano
Summary: Inflammatory bowel diseases are associated with hematological malignancies and the inflammatory environment may contribute to the growth of specific mutated genes in hematopoietic clones.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Huijuan Dou, Andriana Kotini, Wenli Liu, Trevor Fidler, Kaori Endo-Umeda, Xiaoli Sun, Malgorzata Olszewska, Tong Xiao, Sandra Abramowicz, Mustafa Yalcinkaya, Brian Hardaway, Sotirios Tsimikas, Xuchu Que, Alexander Bick, Conor Emdin, Pradeep Natarajan, Eirini P. Papapetrou, Joseph L. Witztum, Nan Wang, Alan R. Tall
Summary: Hematopoietic Lnk deficiency promotes NETosis and arterial thrombosis. Individuals carrying the JAK2(VF) mutation along with the LNK R262W allele are at increased risk of coronary artery disease.
Article
Genetics & Heredity
Olivier Ariste, Pierre de la Grange, Reiner A. Veitia
Summary: Clonal hematopoiesis refers to the abnormal expansion of a hematopoietic stem cell with advantageous somatic variants. A survey found that some common gene mutations have higher frequencies in various populations and are enriched in specific populations. The age distribution of individuals with these variants suggests a potential involvement in clonal hematopoiesis, and the variant allele frequencies in blood DNA of elderly individuals are lower than expected. This can result in misclassification of somatic variants in cancer-predisposition genes, which has consequences for affected individuals and their families.
Review
Hematology
Patrick Stelmach, Andreas Trumpp
Summary: A major challenge in treating acute myeloid leukemia (AML) is the presence of therapy-resistant cells, known as leukemic stem cells (LSC), which can contribute to relapse after achieving remission. LSC display significant plasticity and can develop mechanisms to resist treatment, making them difficult to target with chemotherapy. The combination of venetoclax and azacitidine shows promise in targeting AML LSC, but it is still unclear which patients would benefit most from this treatment and how to overcome resistance mechanisms. Clinical trials are underway to investigate LSC susceptibility to first-line therapies and better understand the complex nature of AML. This review discusses the biology of LSC, resistance mechanisms, potential vulnerabilities, and ongoing clinical trial activities related to LSC-targeted therapies.
Article
Cell & Tissue Engineering
Hector Huerga Encabo, Iker Valle Aramburu, Manuel Garcia-Albornoz, Marion Piganeau, Henry Wood, Anna Song, Alessandra Ferrelli, Aneesh Sharma, Carlos M. Minutti, Marie-Charlotte Domart, Despoina Papazoglou, Kristian Gurashi, Miriam Llorian Sopena, Robert Goldstone, Todd Fallesen, Qian Wang, Linda Ariza-McNaughton, Daniel H. Wiseman, Kiran Batta, Rajeev Gupta, Venizelos Papayannopoulos, Dominique Bonnet
Summary: Somatic mutations in hematopoietic stem cells (HSCs) can lead to clonal hematopoiesis (CH) and the production of mutated immune cells, increasing the risk of leukemia and inflammatory diseases. Through genetic engineering and transplantation, researchers found that loss of the TET2 gene in human HSCs resulted in abnormal development and function of neutrophils, leading to heightened inflammatory responses and compact chromatin structure. These findings provide insights into detecting TET2-CH and preventing CH-associated pathologies mediated by neutrophil extracellular traps (NET).
Review
Biochemistry & Molecular Biology
Xiongkai Yu, Ningjing Qian, Yaping Wang
Summary: Clonal hematopoiesis is a prevalent disease associated with all-cause death and has strong associations with cardiovascular disease. This review summarizes the latest research on clonal hematopoiesis, discusses its strong association with accelerated cardiovascular disease, and rationalizes the intervention of clonal hematopoiesis based on existing evidence, which may be beneficial for future treatment.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Cell Biology
Julia Froebel, Theresa Landspersky, Guelce Percin, Christina Schreck, Susann Rahmig, Alessandro Ori, Daniel Nowak, Marieke Essers, Claudia Waskow, Robert A. J. Oostendorp
Summary: The bone marrow environment, known as the niche, plays a vital role in maintaining blood cell formation throughout life. Different types of stress can disrupt the niche, leading to deregulation of hematopoietic stem cells and their function. Both acute and chronic insults can alter the cellular composition and structure of the niche, ultimately affecting hematopoiesis and increasing susceptibility to diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)