Article
Biology
Rafael Jesus Fernandez, Zachary J. G. Gardner, Katherine J. Slovik, Derek C. Liberti, Katrina N. Estep, Wenli Yang, Qijun Chen, Garrett T. Santini, Javier Perez, Sarah Root, Ranvir Bhatia, John W. Tobias, Apoorva Babu, Michael P. Morley, David B. Frank, Edward E. Morrisey, Christopher J. Lengner, F. Brad Johnson
Summary: DC is a rare genetic disorder that causes short telomeres and early onset of age-related diseases. Using iAT2 cells to model, it is shown that shortened telomeres lead to cell senescence and Wnt signaling defects. The study suggests that Wnt agonists may be potential therapies for DC-related pathologies.
Review
Biochemistry & Molecular Biology
Luis F. Z. Batista, Inderjeet Dokal, Roy Parker
Summary: Telomere biology disorders are rare diseases caused by mutations that impair telomere maintenance, leading to clinical manifestations such as bone marrow failure, pulmonary fibrosis, and liver cirrhosis. There are currently no curative therapies for TBD patients, but research on telomerase RNA component has identified potential therapeutic approaches for further investigation in clinical trials.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Hematology
Martin Kirschner, Margherita Vieri, Kim Kricheldorf, Monica S. Ventura Ferreira, Marcin W. Wlodarski, Michaela Schwarz, Stefan Balabanov, Benjamin Rolles, Susanne Isfort, Steffen Koschmieder, Britta Hoechsmann, Jens Panse, Tim H. Bruemmendorf, Fabian Beier
Summary: AD treatment for DKC patients resulted in hematological response, significant increase in telomere length of lymphocytes and granulocytes, and no detection of MDS-related mutations. Pending longer follow-up, AD treatment appears to be an efficient and safe therapy for DKC patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Microbiology
Dominic P. Czekay, Ute Kothe
Summary: H/ACA sRNPs play crucial roles in ribosome synthesis in archaea and eukaryotes, with both shared general architecture and distinct differences in structure and function. Due to higher protein stability in archaea, there is more detailed information on archaeal H/ACA sRNPs compared to eukaryotes. Long-term studies in yeast have provided a better understanding of the biological role of H/ACA sRNPs in eukaryotes during ribosome biogenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Geriatrics & Gerontology
Jordan D. Fuqua, Marcus M. Lawrence, Zachary R. Hettinger, Agnieszka K. Borowik, Parker L. Brecheen, Marcelina M. Szczygiel, Claire B. Abbott, Frederick F. Peelor, Amy L. Confides, Michael Kinter, Sue C. Bodine, Esther E. Dupont-Versteegden, Benjamin F. Miller
Summary: The failure of old muscle to fully recover after disuse is due to impaired protein folding and degradation mechanisms, rather than limitations in protein synthesis.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Hematology
Neelam Giri, Blanche P. Alter, Sharon A. Savage, Pamela Stratton
Summary: Research shows that women with dyskeratosis congenita (DC) and related telomere biology disorders (TBD) may experience adverse impacts on reproductive health, leading to frequent gynaecological problems and pregnancy complications. Women with TBDs would benefit from multidisciplinary, coordinated care by haematology, gynaecology, and maternal-fetal medicine specialists.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Hannah A. Raj, Tsung-Po Lai, Marena R. Niewisch, Neelam Giri, Youjin Wang, Stephen R. Spellman, Abraham Aviv, Shahinaz M. Gadalla, Sharon A. Savage
Summary: Individuals with telomere biology disorders (TBDs) have significantly shortened telomeres in blood cells, which is associated with increased risk of bone marrow failure and reduced survival. The mean telomere length is estimated to be 5 kilobases, but it is the shortest telomeres that indicate cellular senescence. By using the Telomere Shortest Length Assay (TeSLA), it was found that TBD patients have much shorter mean telomere length and an increased number of telomeres less than 3 kilobases. In addition, TBD patients with severe bone marrow failure and multiple organ manifestations have even shorter telomeres.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Marena R. Niewisch, Neelam Giri, Lisa J. McReynolds, Rotana Alsaggaf, Sonia Bhala, Blanche P. Alter, Sharon A. Savage
Summary: This study examined the associations between mode of inheritance in Dyskeratosis congenita related telomere biology disorders (DC/TBDs) and the clinical manifestations and long-term outcomes. The results showed that different modes of inheritance were correlated with different clinical presentations, and they also had an impact on the survival of patients.
Article
Multidisciplinary Sciences
Mengying Hong, Yushen Du, Dongdong Chen, Yuan Shi, Menglong Hu, Kejun Tang, Zhuping Hong, Xiangzhi Meng, Wan Xu, Gaoqi Wu, Yuanyuan Yao, Liubo Chen, Wenteng Chen, Chit Ying Lau, Li Sheng, Tian-Hao Zhang, Haigen Huang, Zheyu Fang, Yong Shen, Fangfang Sun, Jing Qian, Haibin Qu, Shu Zheng, Suzhan Zhang, Kefeng Ding, Ren Sun
Summary: This study systematically investigated the interaction between the bioactive component Martynoside (MAR) and proteins using mRNA display technology. The results revealed that MAR interacts with ribosomal protein L27a (RPL27A), attenuates the cytotoxicity of 5-fluorouracil (5-FU) on bone marrow cells, and improves hematopoiesis by regulating ribosome biogenesis.
Article
Immunology
Benjamin Rolles, Andres Caballero-Oteyza, Michele Proietti, Sigune Goldacker, Klaus Warnatz, Nadezhda Camacho-Ordonez, Seraina Prader, Jana Pachlopnik Schmid, Margherita Vieri, Susanne Isfort, Robert Meyer, Martin Kirschner, Tim H. Bruemmendorf, Fabian Beier, Bodo Grimbacher
Summary: Telomere biology disorders (TBD) are genetic diseases caused by pathogenic variants in genes related to telomere maintenance. TBD can manifest in adulthood and have variable symptoms, making diagnosis complicated. Common variable immunodeficiency (CVID) is an antibody deficiency syndrome caused by dysfunctional B lymphocytes. In our study, we found that approximately 22% of CVID patients carried rare candidate variants in telomere-associated genes. We recommend including all TBD-associated genes in the genetic screening of patients with antibody deficiencies.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
David P. Dannheisig, Jana Baechle, Jasmin Tasic, Marina Keil, Astrid S. Pfister
Summary: Ribosomes are essential for cell growth and survival, and their biogenesis process in nucleoli is controlled by RNA polymerases I-III and various processing factors. Nucleolar stress triggered by impaired ribosome biogenesis can lead to cell cycle arrest and apoptosis, and is used in modern anti-cancer therapies but may also contribute to diverse pathological conditions. Activation of the Wnt/beta-Catenin pathway is observed when nucleolar stress is induced, suggesting a compensatory mechanism to sustain ribosome biogenesis.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Hematology
Jan-Erik Messling, Karl Agger, Kasper L. Andersen, Kristina Kromer, Hanna M. Kuepper, Anders H. Lund, Kristian Helin
Summary: Novel therapies are urgently needed for the treatment of acute myeloid leukemia (AML). A study identified RIOK2 as a potential target for AML treatment, as its loss leads to decreased protein synthesis and apoptosis in leukemic cells.
Article
Genetics & Heredity
Kevin Norris, Amanda J. Walne, Mark J. Ponsford, Kez Cleal, Julia W. Grimstead, Alicia Ellison, Jenna Alnajar, Inderjeet Dokal, Tom Vulliamy, Duncan M. Baird
Summary: Telomere biology disorders are complex clinical conditions caused by mutations in genes related to telomere maintenance. High-throughput STELA (HT-STELA) has been shown to accurately measure telomere lengths in unaffected individuals and mutation carriers, providing important diagnostic and prognostic information for telomeropathies.
Article
Gastroenterology & Hepatology
Young -Jun Choi, Melissa S. Kim, Joshua H. Rhoades, Nicolette M. Johnson, Corbett T. Berry, Sarah Root, Qijun Chen, Yuhua Tian, Rafael J. Fernandez III, Zvi Cramer, Stephanie Adams-Tzivelekidis, Ning Li, F. Brad Johnson, Christopher J. Lengner
Summary: Critical telomere shortening in dyskeratosis congenita hepatocytes leads to cell-autonomous hyperplasia and activation of hepatic stellate cells in hepatostellate organoids. Dyskeratosis congenita phenotypes can be rescued by inhibiting the serine/threonine kinase AKT (protein kinase B).
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Hematology
Aram Niaz, Jia Truong, Annabel Manoleras, Lucy C. Fox, Piers Blombery, Raja S. Vasireddy, Hilda A. Pickett, Julie A. Curtin, Pasquale M. Barbaro, Jonathan Rodgers, John Roy, Lisa G. Riley, Jessica K. Holien, Scott B. Cohen, Tracy M. Bryan
Summary: Telomere biology disorders (TBDs) are inherited disorders characterized by bone marrow failure. This study investigated a patient with compound heterozygous variants in the TERT gene and found functional interaction between the proteins encoded by the two alleles.