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
Medicine, General & Internal
Veronica Judith Picos-Cardenas, Saul Armando Beltran-Ontiveros, Jose Alfonso Cruz-Ramos, Jose Alfredo Contreras-Gutierrez, Eliakym Arambula-Meraz, Carla Angulo-Rojo, Alma Marlene Guadron-Llanos, Emir Adolfo Leal-Leon, Dora Maria Cedano-Prieto, Juan Pablo Meza-Espinoza
Summary: This case report describes a female patient with typical symptoms of dyskeratosis congenita and identifies a novel mutation in the TINF2 gene as the cause of the disease through genetic and molecular biology studies.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Biology
Kentaro Nakashima, Yuya Kunisaki, Kentaro Hosokawa, Kazuhito Gotoh, Hisayuki Yao, Ryosuke Yuta, Yuichiro Semba, Jumpei Nogami, Yoshikane Kikushige, Patrick S. Stumpf, Ben D. MacArthur, Dongchon Kang, Koichi Akashi, Shouichi Ohga, Fumio Arai
Summary: Protection of telomeres 1a (POT1a) is crucial for maintaining the stability of the bone marrow microenvironment and supporting B-lymphopoiesis. Deletion of POT1a in mesenchymal stem cells (MSCs) may lead to bone marrow dysfunction and myeloid skewing.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jesus Garcia-Castillo, Francisca Alcaraz-Perez, Elena Martinez-Balsalobre, Diana Garcia-Moreno, Marlies P. Rossmann, Miriam Fernandez-Lajarin, Manuel Bernabe-Garcia, Ana B. Perez-Oliva, Virginia C. Rodriguez-Cortez, Clara Bueno, Isaac Adatto, Suneet Agarwal, Pablo Menendez, Leonard Zon, Victoriano Mulero, Maria L. Cayuela
Summary: Dyskeratosis congenita (DC) is a rare genetic syndrome caused by mutations in telomerase or telomeric proteins. Research shows that zebrafish terc plays a crucial role in regulating the expression of master myeloid genes, while mutations found in DC patients affect this process.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
Medicine, Research & Experimental
Lingling Liu, Danfeng Zhang, Qiuhao Fu, Jingdi Wang, Jifeng Yu, Dandan Chen, Fang Wang, Rong Guo, Xinsheng Xie, Zhongxing Jiang, Yingmei Li
Summary: Aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells and progenitor cells. Recent research has shown somatic mutations in AA patients, but the impact of these mutations remains uncertain. A retrospective study was conducted on AA and myelodysplastic syndromes (MDS) patients, revealing different gene mutation patterns between the two groups, with a lower mutation frequency in AA patients.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Hematology
Samantha Nichele, Carmem Bonfim, G. D. Luiz Jr, Gisele Loth, Cilmara Kuwahara, Joanna Trennephol, Vaneuza A. M. Funke, Daniela E. Marinho, Adriana Koliski, Adriana M. Rodrigues, Rebeca T. G. Mousquer, Anders Fasth, Alberto C. M. Lima, Rodrigo T. Calado, Ricardo Pasquini
Summary: This retrospective study describes the outcomes of hematopoietic cell transplantation in patients with telomere biology diseases (TBD) between 1993 and 2019. The study found that although transplantation is a curative treatment option, non-hematological phenotypes remain a major challenge and are associated with poor long-term follow-up outcomes.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Szymon Janczar, Martin Kirschner, Fabian Beier, Tim H. Bruemmendorf, Marek Ussowicz, Katarzyna Babol-Pokora, Aleksandra Oszer, Ayami Yoshimi, Krzysztof Kalwak, Wojciech Mlynarski
Summary: Dyskeratosis congenita is a bone marrow failure syndrome with telomere biology abnormalities. A boy with a rare TERT gene variant presented with juvenile myelomonocytic leukemia.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Pediatrics
M. L. Uria-Oficialdegui, S. Navarro, L. Murillo-Sanjuan, C. Rodriguez-Vigil, M. I. Benitez-Carbante, C. Blazquez-Goni, J. A. Salinas, C. Diaz-de-Heredia
Summary: This study describes the natural history of dyskeratosis congenita (DC) through a cohort of patients diagnosed in childhood and followed up for a long period of time. Results showed that DC patients had hematologic manifestations at diagnosis, and some developed mucocutaneous manifestations during the first decade of life. Bone marrow failure was observed in a majority of patients, and hematopoietic stem cell transplant was performed in some cases. Overall, DC was associated with high morbidity and mortality, highlighting the importance of multidisciplinary follow-up and transition to adult care.
FRONTIERS IN PEDIATRICS
(2023)
Review
Hematology
Inderjeet Dokal, Hemanth Tummala, Tom Vulliamy
Summary: Inherited bone marrow failure syndromes are a group of diseases characterized by diverse manifestations and involvement of bone marrow failure. Significant progress has been made in the genetics of these diseases, revealing how genetic mutations disrupt normal hematopoiesis. Furthermore, these studies provide insights into human development and cancer. Genetic testing facilitates accurate diagnosis in clinical practice. Current treatment options have improved patient outcomes, but managing certain complications remains challenging.
Article
Oncology
Hongchen Liu, Xiaoli Zheng, Chengtao Zhang, Jiajun Xie, Beibei Gao, Jing Shao, Yan Yang, Hengxiang Wang, Jinsong Yan
Summary: The study demonstrated the efficacy of haploidentical bone marrow transplantation (haplo-BMT) for patients with severe aplastic anemia II (SAA-II), achieving a 3-year overall survival and disease-free survival rate of 86.4% +/- 0.73%. This indicates that haplo-BMT could be considered as an alternative treatment strategy for SAA-II patients lacking HLA-matched donors.
FRONTIERS OF MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Xing-An Wang, Ju-Pi Li, Kang-Hsi Wu, Shun-Fa Yang, Yu-Hua Chao
Summary: Aplastic anemia is a rare but life-threatening disease characterized by low blood cell count and reduced cellularity in the bone marrow. Mesenchymal stem cell dysfunction is believed to play a role in the development of the disease. This review provides a comprehensive understanding of the involvement of mesenchymal stem cells in acquired idiopathic aplastic anemia and discusses their clinical application. The pathophysiology of the disease, properties of mesenchymal stem cells, and results of mesenchymal stem cell therapy in animal models are also described. The authors anticipate that more patients with aplastic anemia can benefit from mesenchymal stem cell therapy in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Surbhi Agrawal, P. Mahesh Shanmugam, Payal Naresh Shah, Divyansh Kailashchandra Mishra, Rajesh Ramanjulu
Summary: This study reports a case of Revesz syndrome, characterized by bone marrow failure, exudative retinopathy, and other systemic features. Genetic testing confirmed the diagnosis of Revesz syndrome.
OPHTHALMIC SURGERY LASERS & IMAGING RETINA
(2022)
Article
Pediatrics
Liqing Wang, Jianwei Li, Qiuhong Xiong, Yong-An Zhou, Ping Li, Changxin Wu
Summary: This study reports the first discovery of a DKC1 gene mutation in a Chinese family, which is associated with the phenotype of mucocutaneous triad. The findings broaden the understanding of disease variation, genotype-phenotype correlations, and facilitate clinical diagnosis of DC in China.
FRONTIERS IN PEDIATRICS
(2022)
Letter
Oncology
Christopher G. Tomlinson, Ghadir Sasa, Geraldine Aubert, Bailey Martin-Giacalone, Sharon E. Plon, Tracy M. Bryan, Alison A. Bertuch, Maria M. Gramatges
Article
Oncology
Viviane C. Cahen, Yimei Li, Kelly D. Getz, Caitlin W. Elgarten, Amanda M. DiNofia, Jennifer J. Wilkes, Lena E. Winestone, Yuan-Shung Huang, Tamara P. Miller, M. Monica Gramatges, Karen R. Rabin, Brian T. Fisher, Richard Aplenc, Alix E. Seif
Summary: This study focused on accurately identifying and evaluating relapse and hematopoietic stem cell transplantation (HSCT) occurrences in children with acute lymphoblastic leukemia (ALL) using administrative data. By utilizing the PHIS database and chart reviews at two hospitals, the study demonstrated that the method was effective in identifying relapse and HSCT, while also estimating their incidences.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Pediatrics
Ryan W. Himes, Eric H. Chiou, Karen Queliza, Dror S. Shouval, Raz Somech, Suneet Agarwal, Kunal Jajoo, David S. Ziegler, Christian P. Kratz, James Huang, Tiffany L. Lucas, Kasiani C. Myers, Adam S. Nelson, Courtney D. DiNardo, Blanche P. Alter, Neelam Giri, Payal P. Khincha, Lisa J. McReynolds, Carlo Dufour, Filomena Pierri, Frederick D. Goldman, Youmna Sherif, Sharon A. Savage, Tamir Miloh, Alison A. Bertuch
Summary: Gastrointestinal hemorrhage in patients with telomere biology disorders is associated with significant morbidity, with vascular ectasias rather than varices being common, and the overall long-term outcome for affected patients is poor.
JOURNAL OF PEDIATRICS
(2021)
Article
Multidisciplinary Sciences
Alyssa L. Kennedy, Kasiani C. Myers, James Bowman, Christopher J. Gibson, Nicholas D. Camarda, Elissa Furutani, Gwen M. Muscato, Robert H. Klein, Kaitlyn Ballotti, Shanshan Liu, Chad E. Harris, Ashley Galvin, Maggie Malsch, David Dale, John M. Gansner, Taizo A. Nakano, Alison Bertuch, Adrianna Vlachos, Jeffrey M. Lipton, Paul Castillo, James Connelly, Jane Churpek, John R. Edwards, Nobuko Hijiya, Richard H. Ho, Inga Hofmann, James N. Huang, Sioban Keel, Adam Lamble, Bonnie W. Lau, Maxim Norkin, Elliot Stieglitz, Wendy Stock, Kelly Walkovich, Steffen Boettcher, Christian Brendel, Mark D. Fleming, Stella M. Davies, Edie A. Weller, Christopher Bahl, Scott L. Carter, Akiko Shimamura, R. Coleman Lindsley
Summary: Research on germline genetic leukemia predisposition in Shwachman-Diamond syndrome identified early emergence of multiple hematopoietic clones with EIF6 or TP53 mutations. The germline SBDS deficiency constrains clone selection via compensatory EIF6 inactivation and maladaptive TP53 mutations, with subsequent leukemia linked to biallelic TP53 alterations. These findings offer insights into clinical surveillance strategies.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Elissa Furutani, Shanshan Liu, Ashley Galvin, Sarah Steltz, Maggie M. Malsch, Sara K. Loveless, Leann Mount, Jordan H. Larson, Kelan Queenan, Alison A. Bertuch, Mark D. Fleming, John M. Gansner, Amy E. Geddis, Rabi Hanna, Sioban B. Keel, Bonnie W. Lau, Jeffrey M. Lipton, Robert Lorsbach, Taizo A. Nakano, Adrianna Vlachos, Winfred C. Wang, Stella M. Davies, Edie Weller, Kasiani C. Myers, Akiko Shimamura
Summary: The study examined 153 subjects with SDS and found that absolute neutrophil counts and hemoglobin levels increase with age, while platelet counts and marrow cellularity decrease. Marrow cellularity was not correlated with blood counts. 17% of subjects developed myeloid malignancies.
Article
Genetics & Heredity
Runjun D. Kumar, Mustafa Tosur, Seema R. Lalani, Donald H. Mahoney, Alison A. Bertuch
Summary: This study reports a patient with red cell aplasia, intellectual disability, and other symptoms, who carries a germline variation in the TP53 gene that can activate the transcription factor. This case adds to the understanding of the clinical disease associated with such variations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Hematology
Seunga Choo, Franziska K. Lorbeer, Samuel G. Regalado, Sarah B. Short, Shannon Wu, Gabrielle Rieser, Alison A. Bertuch, Dirk Hockemeyer
Summary: Mutations in the TINF2 gene cause telomere shortening and BM failure syndrome. This study introduces TIN2-DC mutations in hESCs and HSPCs to understand the disease mechanism and develop therapeutic strategies. The study demonstrates that editing the mutant TINF2 allele restores telomere length and replicative potential in stem cells. The findings provide a versatile platform for evaluating potential therapeutic approaches for BM failure.
Article
Oncology
Priyadarshani Dharia, Michael D. Swartz, M. Brooke Bernhardt, Han Chen, M. Monica Gramatges, Philip J. Lupo, Austin L. Brown, Michael E. Scheurer
Summary: This study retrospectively analyzed 548 patients with acute lymphoblastic leukemia and found that older age, overweight, and treatment intensity increased the risk of pegaspargase-associated toxicities.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Elizabeth E. Dong, Michael A. Bruno, Jeffrey J. Kim, Melanie B. Bernhardt, Austin L. Brown, Maria M. Gramatges
Summary: Tyrosine kinase inhibitors (TKIs) have improved prognosis for pediatric leukemia, but this study suggests that TKI exposure may lead to late-onset complications. The results indicate that children receiving TKI treatment may face long-term health risks.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Oncology
Rachel D. Harris, Melissa A. Richard, Maria Monica J. Gramatges, Kevin Wilhelm, Michael E. Scheurer, Philip J. Lupo, Austin L. Brown
Summary: Survivors of childhood central nervous system tumors may experience early-onset aging-related phenotypes. DNA methylation age, as an emerging biomarker, can predict the chronic health conditions of long-term survivors. This study explores the epigenetic age acceleration in survivors of pediatric CNS tumors using blood samples collected post-diagnosis.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2023)
Review
Genetics & Heredity
Patrick Revy, Caroline Kannengiesser, Alison A. Bertuch
Summary: This article reviews the confirmed and potential genes causing telomere diseases and describes their main functions in telomere biology. The authors also discuss the genetic features underlying the complexity of these diseases.
NATURE REVIEWS GENETICS
(2023)
Article
Medicine, Research & Experimental
Timothy S. Olson, Benjamin F. Frost, Jamie L. Duke, Marian Dribus, Hongbo M. Xie, Zachary D. Prudowsky, Elissa Furutani, Jonas Gudera, Yash B. Shah, Deborah Ferriola, Amalia Dinou, Ioanna Pagkrati, Soyoung Kim, Yixi Xu, Meilun He, Shannon Zheng, Sally Nijim, Ping Lin, Chong Xu, Taizo A. Nakano, Joseph H. Oved, Beatriz M. Carreno, Yung-Tsi Bolon, Shahinaz M. Gadalla, Steven Ge Marsh, Sophie Paczesny, Stephanie J. Lee, Dimitrios S. Monos, Akiko Shimamura, Alison A. Bertuch, Loren Gragert, Stephen R. Spellman, Daria Babushok
Summary: This study evaluated somatic HLA loss in patients with acquired aplastic anemia (AA) and identified HLA alleles associated with the development of AA. The results showed that HLA alleles increase the risk of AA, but do not affect response to immunosuppression or transplant outcomes. Higher pathogenicity alleles are associated with higher rates of clonal evolution in AA patients.
Editorial Material
Hematology
Maria Monica Gramatges
Article
Oncology
Melissa A. Richard, Sogol Mostoufi-Moab, Nisha Rathore, Jessica Baedke, Austin L. Brown, Stephen J. Chanock, Danielle N. Friedman, Monica Gramatges, Rebecca M. Howell, Kala Y. Kamdar, Wendy M. Leisenring, Lillian R. Meacham, Lindsay M. Morton, Kevin Oeffinger, Leslie L. Robison, Yadav Sapkota, Charles A. Sklar, Gregory T. Armstrong, Smita Bhatia, Philip J. Lupo
Summary: This study aimed to evaluate the genetic risk factors of diabetes mellitus among childhood cancer survivors. A novel diabetes locus was identified among survivors not exposed to abdominal radiation. Risk prediction models showed moderate accuracy in predicting diabetes among survivors.
JCO PRECISION ONCOLOGY
(2022)