{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:44:18Z","timestamp":1789015458877,"version":"build-2803163510"},"reference-count":50,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA194547"],"award-info":[{"award-number":["R01 CA194547"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,9,13]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although advance has been made in understanding the pathogenesis of mature T-cell neoplasms, the initiation and progression of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), remain poorly understood. A subset of AITL\/PTCL-NOS patients develop concomitant hematologic neoplasms (CHN), and a biomarker to predict this risk is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We generated and analyzed the mutation profiles through 537-gene targeted sequencing of the primary tumors and matched bone marrow\/peripheral blood samples in 25 patients with AITL and two with PTCL-NOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Clonal hematopoiesis (CH)-associated genomic alterations, found in 70.4% of the AITL\/PTCL-NOS patients, were shared among CH and T-cell lymphoma, as well as concomitant myeloid neoplasms or diffuse large B-cell lymphoma (DLBCL) that developed before or after AITL. Aberrant AID\/APOBEC activity-associated and tobacco smoking-associated mutational signatures were respectively enriched in the early CH-associated mutations and late non-CH-associated mutations during AITL\/PTCL-NOS development. Moreover, analysis showed that the presence of CH harboring \u22652 pathogenic TET2 variants with \u226515% of allele burden conferred higher risk for CHN (p=0.0006, hazard ratio = 14.01, positive predictive value = 88.9%, negative predictive value = 92.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We provided genetic evidence that AITL\/PTCL-NOS, CH, and CHN can frequently arise from common mutated hematopoietic precursor clones. Our data also suggests smoking exposure as a potential risk factor for AITL\/PTCL-NOS progression. These findings provide insights into the cell origin and etiology of AITL and PTCL-NOS and provide a novel stratification biomarker for CHN risk in AITL patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>R01 grant (CA194547) from the National Cancer Institute to WT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.66395","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T20:00:23Z","timestamp":1632772823000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66395","source":"Crossref","is-referenced-by-count":36,"title":["Mutation analysis links angioimmunoblastic T-cell lymphoma to clonal hematopoiesis and smoking"],"prefix":"10.7554","volume":"10","author":[{"given":"Shuhua","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genomics Resources Core Facility, Weill Cornell Medicine","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Inghirami","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4283-0005","authenticated-orcid":true,"given":"Wayne","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1126\/science.aag0299","article-title":"Mutational signatures associated with tobacco smoking in human cancer","volume":"354","author":"Alexandrov","year":"2016","journal-title":"Science"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1182\/blood.v99.2.627","article-title":"Neoplastic T cells in angioimmunoblastic t-cell lymphoma express cd10","volume":"99","author":"Attygalle","year":"2002","journal-title":"Blood"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.ccr.2013.04.011","article-title":"EZH2 is required for germinal center formation and somatic ezh2 mutations promote lymphoid transformation","volume":"23","author":"B\u00e9guelin","year":"2013","journal-title":"Cancer Cell"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1182\/blood-2005-12-4852","article-title":"Genetic and clinical implications of the val617phe jak2 mutation in 72 families with myeloproliferative disorders","volume":"108","author":"Bellann\u00e9-Chantelot","year":"2006","journal-title":"Blood"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.1158\/0008-5472.CAN-09-0015","article-title":"Genetic mutations associated with cigarette smoking in pancreatic cancer","volume":"69","author":"Blackford","year":"2009","journal-title":"Cancer Research"},{"key":"bib7","first-page":"744","article-title":"Disparities in secondhand smoke exposure--united states, 1988-1994 and 1999-2004","volume":"57","author":"Centers for Disease Control and Prevention (CDC)","year":"2008","journal-title":"MMWR. 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