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)
Article
Cell Biology
Chong Zhang, Rui Huang, Xirui Ma, Jiehui Chen, Xinlu Han, Li Li, Lingfei Luo, Hua Ruan, Honghui Huang
Summary: Ribosome biogenesis is crucial in cells, and abnormalities can lead to diseases. Disruptions in animals can harm embryonic development, affecting digestive organs and hematopoiesis. Loss of function in ribosome biogenesis genes often causes abnormalities, including those related to P53 in zebrafish embryos.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jeanne Rakotopare, Franck Toledo, Alfonso Baldi
Summary: Studies on both animal models and humans have revealed that mutations affecting p53 activity can lead to features of certain bone marrow failure syndromes, including dyskeratosis congenita, Diamond-Blackfan anemia, and Fanconi anemia. p53 regulates multiple genes related to these syndromes, forming a positive feedback loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ji Hoon Han, Gavin Ryan, Alyson Guy, Lu Liu, Mathieu Quinodoz, Ingrid Helbling, Joey E. Lai-Cheong, Julian Barwell, Marc Folcher, John A. McGrath, Celia Moss, Carlo Rivolta
Summary: The study identified LIPHAK as a previously unrecognized ribosomopathy, where variants in the LTV1 gene result in abnormal splicing and premature termination of the protein it encodes.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Michele Callea, Diego Martinelli, Francisco Cammarata-Scalisi, Chiara Grimaldi, Houweyda Jilani, Piercesare Grimaldi, Colin Eric Willoughby, Antonino Morabito
Summary: Dyskeratosis congenita is a genetic syndrome with diverse clinical manifestations, including bone marrow failure and tumors. This review discusses the clinical characteristics, molecular genetics, disease progression, treatment options, and differential diagnosis of the disease, providing personalized medical assessment and family genetic counseling.
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
Cell Biology
Deena Iskander, Guanlin Wang, Elisabeth F. Heuston, Chrysi Christodoulidou, Bethan Psaila, Kanagaraju Ponnusamy, Hongwei Ren, Zeinab Mokhtari, Mark Robinson, Aristeidis Chaidos, Pritesh Trivedi, Nikolaos Trasanidis, Alexia Katsarou, Richard Szydlo, Carmen G. Palii, Mehmood H. Zaidi, Qais Al-Oqaily, Valentina S. Caputo, Anindita Roy, Yvonne Harrington, Leena Karnik, Kikkeri Naresh, Adam J. Mead, Supat Thongjuea, Marjorie Brand, Josu de la Fuente, David M. Bodine, Irene Roberts, Anastasios Karadimitris
Summary: The study investigates how mutations in ribosomal protein genes affect erythroid progenitor development in Diamond-Blackfan anemia, with RPS-DBA showing erythroid differentiation arrest and RPL-DBA exhibiting relatively preserved abnormal erythroid progenitors and precursors. The findings suggest distinct mechanisms of erythroid failure and phenotype-genotype correlations in DBA, which may aid in identifying therapeutic targets.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Nozomu Kawashima, Valentino Bezzerri, Seth J. Corey
Summary: Hereditary bone marrow failure syndromes (IBMFSs) are a group of rare genetic disorders, including Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia, and others. Mutations in specific genes involved in DNA damage response, ribosome structure or assembly, or telomere maintenance are responsible for the development of these syndromes. This review discusses the pathogenetic mechanisms of IBMFSs and proposes a potential role for pro-inflammatory cytokines in mediating cytopenias and the transformation to myeloid neoplasia. Anti-inflammatory therapies may hold promise in the treatment of these disorders.
Article
Oncology
Haider Nisar, Memoona Khan, Qamar Un Nisa Chaudhry, Raheel Iftikhar, Tariq Ghafoor
Summary: Dyskeratosis congenita (DKC) is a genetic disorder characterized by leukoplakia, nail dystrophy, and reticular hyperpigmentation. Mutations in genes such as DKC1, TINF2, TERC, TERT, C16orf57, NOLA2, NOLA3, WRAP53/TCAB1, and RTEL1 have been linked to DKC. We report a novel homozygous variant of RTEL1, c.2060C>T (p.Ala687Val), in a DKC patient, which may be considered diagnostic for DKC in a Pakistani population.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Mone't B. Thompson, Daniel Muldoon, Kelvin C. de Andrade, Neelam Giri, Blanche P. Alter, Sharon A. Savage, Robert D. Shamburek, Payal P. Khincha
Summary: The study found that oral androgen therapy in DC patients altered lipid and lipoprotein levels, potentially increasing the risk of atherogenic cardiovascular disease. Individuals on androgens for DC-related BMF should undergo cardiovascular disease monitoring.
Article
Developmental Biology
Yimei Dai, Shuting Wu, Canran Cao, Rongtao Xue, Xuefen Luo, Zilong Wen, Jin Xu
Summary: Through studying zebrafish, we have discovered a surprising role of Csf1rb in maintaining the pool of hematopoietic stem and progenitor cells (HSPCs). This study reveals a novel function of Csf1r in maintaining HSPCs, independently of known ligands.
Letter
Medicine, Research & Experimental
Saeed Dorgaleleh, Karim Naghipoor, Amir Hozhabrpour, Hassan Vahidnezhad
Summary: Dyskeratosis Congenita (DC) is a rare and heterogeneous disease with shorter telomere length. Studies have shown that individuals with a short telomere background are more likely to experience severe symptoms and higher mortality rate related to COVID-19. This study hypothesized that patients with DC are at a higher risk of developing symptomatic COVID-19 requiring further clinical care.
MEDICAL HYPOTHESES
(2022)
Article
Endocrinology & Metabolism
Z. Belaya, O. Golounina, A. Nikitin, N. Tarbaeva, E. Pigarova, E. Mamedova, M. Vorontsova, I. Shafieva, I. Demina, W. Van Hul
Summary: A young male patient with clinical signs of dyskeratosis congenita presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing revealed a previously unreported mutation in the PARN gene. Treatment with zoledronic acid was effective at preventing further fractures.
OSTEOPOROSIS INTERNATIONAL
(2021)
Article
Hematology
Christopher R. Reilly, Mikko Myllymaki, Robert Redd, Shilpa Padmanaban, Druha Karunakaran, Valerie Tesmer, Frederick D. Tsai, Christopher J. Gibson, Huma Q. Rana, Liang Zhong, Wael Saber, Stephen R. Spellman, Zhen-Huan Hu, Esther H. Orr, Maxine M. Chen, Immaculata De Vivo, Daniel J. DeAngelo, Corey Cutler, Joseph H. Antin, Donna Neuberg, Judy E. Garber, Jayakrishnan Nandakumar, Suneet Agarwal, R. Coleman Lindsley
Summary: Research indicates that rare TERT variants are associated with an increased risk of developing MDS and nonrelapse mortality, with 90% of the variants showing impairment in telomere elongation function. Routine screening for TERT rare variants in MDS patients may enhance transplant outcomes.
Article
Cell Biology
Andrea Ditadi, Christopher M. Sturgeon, Joanna Tober, Geneve Awong, Marion Kennedy, Amanda D. Yzaguirre, Lisa Azzola, Elizabeth S. Ng, Edouard G. Stanley, Deborah L. French, Xin Cheng, Paul Gadue, Nancy A. Speck, Andrew G. Elefanty, Gordon Keller
NATURE CELL BIOLOGY
(2015)
Article
Biochemical Research Methods
Andrea Ditadi, Christopher M. Sturgeon
Review
Cell Biology
Andrea Ditadi, Christopher M. Sturgeon, Gordon Keller
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Carissa Dege, Christopher M. Sturgeon
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2017)
Article
Geriatrics & Gerontology
Zhen Yu, Rong Wang, Wilson C. Fok, Alexander Coles, Adam B. Salmon, Viviana I. Perez
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2015)
Editorial Material
Cell & Tissue Engineering
Christopher M. Sturgeon, Andrea Ditadi
Article
Hematology
Wilson Chun Fok, Siddharth Shukla, Alexandre Teixeira Vessoni, Kirsten Ann Brenner, Roy Parker, Christopher M. Sturgeon, Luis Francisco Zirnberger Batista
Article
Cell Biology
Carissa Dege, Katherine H. Fegan, J. Philip Creamer, Melissa M. Berrien-Elliott, Stephanie A. Luff, Darren Kim, Julia A. Wagner, Paul D. Kingsley, Kathleen E. McGrath, Todd A. Fehniger, James Palis, Christopher M. Sturgeon
DEVELOPMENTAL CELL
(2020)
Article
Cell Biology
Stephanie A. Luff, J. Philip Creamer, Sara Valsoni, Carissa Dege, Rebecca Scarfo, Analisa Dacunto, Sara Cascione, Lauren N. Randolph, Eleonora Cavalca, Ivan Merelli, Samantha A. Morris, Andrea Ditadi, Christopher M. Sturgeon
Summary: Luff et al. discovered a distinct human mesoderm cell population that generates mature haemogenic endothelium in a retinoic acid-dependent manner. This finding highlights the importance of retinoic acid-responsive mesoderm in haematopoietic ontogeny. The revised model of human haematopoietic development provides essential resolution to the regulation and origins of the multiple waves of haematopoiesis.
NATURE CELL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
J. Philip Creamer, Stephanie A. Luff, Hao Yu, Christopher M. Sturgeon
Summary: The expression of CDX4+CD1d+ marks an early progenitor of hematopoietic endothelium with intra-embryonic-like potential in early mesoderm, providing important insights for the study of human hematopoietic development and potential improvements in hematopoietic differentiation conditions for regenerative medicine applications.
STEM CELL RESEARCH
(2022)
Editorial Material
Hematology
Andrea Ditadi, Christopher M. Sturgeonb
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Ho-Chang Jeong, Siddharth Shukla, Wilson Chun Fok, Thao Ngoc Huynh, Luis Francisco Zirnberger Batista, Roy Parker
Summary: Mutations in the USB1 gene result in hematopoietic failure in patients with poikiloderma with neutropenia. The exact mechanism behind this condition has not been determined, as pre-mRNA splicing remains unaffected. In this study, human embryonic stem cells with the PN-associated mutation in USB1 were generated, and it was found that dysregulated microRNA levels contribute to the hematopoietic failure. Inhibition of PAPD5/7, enzymes responsible for adding 3'-end adenylated tails, rescued hematopoiesis in USB1 mutants, suggesting it as a potential therapy for PN.
Article
Hematology
J. Philip Creamer, Carissa Dege, Qihao Ren, Jolie T. K. Ho, Mark C. Valentine, Todd E. Druley, Christopher M. Sturgeon