{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sande CM"],"funding":["National Institute of Allergy and Infectious Diseases","Team Telomere and the Penn Orphan Disease Center","Uplifting Athletes and Team Telomere","NIAID NIH HHS","NHLBI NIH HHS","National Heart, Lung, and Blood Institute","NHGRI NIH HHS","American Society of Hematology","National Human Genome Research Institute","Edward P. Evans Foundation","Farmor Foundation","Leukemia and Lymphoma Society"],"pagination":["e181659"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11996883"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(8)"],"pubmed_abstract":["Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% of patients, including 20 presumed loss-of-function va"],"journal":["The Journal of clinical investigation"],"pubmed_title":["ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders."],"pmcid":["PMC11996883"],"funding_grant_id":["N/A","K01HL155231","5R01HL131744","R01 HL148821","T32 AI055413","AI 055413-19","T32 HG009495","L70 HL175832","2T32HG009495-06","5R01HL148821","K01 HL155231","R01 HL131744"],"pubmed_authors":["Link DC","Lin P","Bowman M","Agarwal S","Cheng JM","Sande CM","Morrissette JJ","Kumar S","Stanley NL","Lindsley RC","Lapite A","Guo K","Gill S","Dokal I","Chen S","Shestova O","Abraham DM","Corines J","Yang G","Chen Q","Olson TS","Gelman AE","Dutta R","Nicholas P","Zheng S","Freeman C","Oetjen KA","Johnson FB","Taylor DM","Peterson M","Churpek JE","Rosenheck JP","Bowman RL","Banaszak LG","Reilly CR","Shoger KN","Mitchell DV","Zheng J","Deolikar RJ","Tague LK","Bertuch AA","Hausler R","Zhou M","Munkhbileg B","Smith-Simmer K","Lieberman DB","Reinig EF","Babushok DV","Walne AJ","Gebhard T","Brundige KJ"],"additional_accession":[]},"is_claimable":false,"name":"ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders.","description":"Telomere biology disorders (TBDs) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. Of these patients, 47.6% (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% of patients, including 20 presumed loss-of-function va","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-05-29T17:10:46.664Z","creation":"2025-07-10T03:08:29.151Z"},"accession":"S-EPMC11996883","cross_references":{"pubmed":["40179146"],"doi":["10.1172/JCI181659"]}}