{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:00:22Z","timestamp":1785214822380,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Germline predisposition gene mutations may influence outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study of 558 patients undergoing HSCT (allo-HSCT in 557 cases, auto-HSCT in 1 case) evaluated the impact of germline predisposition gene mutations on outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Enrichment of\n                      <jats:italic>HAVCR2<\/jats:italic>\n                      mutations in B-NHL and\n                      <jats:italic>UNC13D<\/jats:italic>\n                      mutations in MDS was associated with poorer prognosis. While homozygous mutation carriers (7.5%) overall did not have reduced survival, their outcomes were significantly better with unrelated versus related donors (3-year DFS\/OS: 82.1% vs. 48.3%\/56.7%). Mutations in genes linked to inborn errors of immunity affecting both cellular and humoral immunity (IACHI) predicted inferior survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Germline mutations, particularly in IACHI-related genes, influence HSCT outcomes. Pre-transplant genetic screening and opting for unrelated donors for homozygous carriers may optimize transplantation strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1880348","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:43Z","timestamp":1785212803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of germline predisposition genes to hematologic malignancies on transplant outcomes and donor selection"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhihui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostic Laboratory, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostic Laboratory, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyang","family":"Ming","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhi","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinlong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostic Laboratory, Beijing Gobroad Boren Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"652","DOI":"10.20944\/preprints202311.0482.v1","article-title":"Germline variants and characteristic features of hereditary hematological Malignancy syndrome","volume":"25","author":"Arai","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2025.08.002","article-title":"Germline predispositions to myeloid Malignancies: Across the lifespan","volume":"62","author":"Atluri","year":"2025","journal-title":"Semin Hematol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3892\/ijo.2025.5809","article-title":"Emerging insights into alternative end-joining: Mechanisms, genome instability and therapeutic opportunities in cancer (review)","volume":"67","author":"Azam","year":"2025","journal-title":"Int J Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2025.02.007","article-title":"Clinical management of three JMML siblings with germline CBL variation","author":"Agaoglu","year":"2025","journal-title":"Cancer Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052638","article-title":"Hematopoietic stem-cell transplantation","volume":"354","author":"Copelan","year":"2006","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0047","article-title":"Hematopoietic cell transplantation, version 3.2025, NCCN clinical practice guidelines in oncology","volume":"23","author":"Loren","year":"2025"},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.1016\/j.mayocp.2019.12.013","article-title":"Hereditary predisposition to hematopoietic neoplasms: When bloodline matters for blood cancers","volume":"95","author":"Mangaonkar","year":"2020","journal-title":"Mayo Clin Proc"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.72.6745","article-title":"Practical implications of the 2016 revision of the World Health Organization classification of lymphoid and myeloid neoplasms and acute leukemia","volume":"35","author":"Leonard","year":"2017","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0452-6","article-title":"Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma","volume":"33","author":"Pertesi","year":"2019","journal-title":"Leukemia"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-17-1900","article-title":"Germline lysine-specific demethylase 1 (LSD1\/KDM1A) mutations confer susceptibility to multiple myeloma","volume":"78","author":"Wei","year":"2018","journal-title":"Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26321","article-title":"Spectrum of hematological Malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes","volume":"96","author":"Martin","year":"2021","journal-title":"Am J Hematol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","article-title":"Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors","volume":"18","author":"Glucksberg","year":"1974","journal-title":"Transplantation"},{"key":"B13","article-title":"1994 consensus conference on acute GVHD grading","volume":"15","author":"Przepiorka","year":"1995","journal-title":"Bone Marrow Transplant"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.09.004","article-title":"National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report","volume":"11","author":"Filipovich","year":"2005","journal-title":"Biol Blood Marrow Transplant"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02199-3","article-title":"The Human Gene Mutation Database (HGMD((R))): Optimizing its use in a clinical diagnostic or research setting","volume":"139","author":"Stenson","year":"2020","journal-title":"Hum Genet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01171-4","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: A policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J ClinImmunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.10.018","article-title":"Donor-derived Malignancy and transplantation morbidity: Risks of patient and donor genetics in allogeneic hematopoietic stem cell transplantation","volume":"30","author":"Williams","year":"2024","journal-title":"Transplant Cell Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2025017084","article-title":"Allogeneic hematopoietic stem cell transplantation in germline DDX41 mutated patients with myeloid Malignancies","volume":"9","author":"Loschi","year":"2025","journal-title":"Blood Adv"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.20196","article-title":"Impact of CHEK2 germline variants on haematological Malignancy risk and outcomes of allogeneic HSCT","volume":"207","author":"Lahtinen","year":"2025","journal-title":"Br J Haematol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101143","article-title":"Unraveling germline predisposition in hematological neoplasms: Navigating complexity in the genomic era","volume":"64","author":"Jerez","year":"2024","journal-title":"Blood Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-201465","article-title":"Genome-first determination of the prevalence and penetrance of eight germline myeloid Malignancy predisposition genes: A study of two population-based cohorts","volume":"39","author":"Hendricks","year":"2025","journal-title":"Leukemia"},{"key":"B23","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41409-022-01828-x","article-title":"Clinically relevant germline variants in allogeneic hematopoietic stem cell transplant recipients","volume":"58","author":"Lahtinen","year":"2023","journal-title":"Bone Marrow Transplant"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.70.8644","article-title":"Germline genetic predisposition to hematologic Malignancy","volume":"35","author":"Furutani","year":"2017","journal-title":"J Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08827.x","article-title":"Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT","volume":"159","author":"Foster","year":"2008","journal-title":"Br J Dermatol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.ajhg.2012.03.013","article-title":"Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis","volume":"90","author":"Jordan","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1653885","article-title":"Protein C deficiency: A database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH","volume":"73","author":"Reitsma","year":"1995","journal-title":"Thromb Haemost"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5208","article-title":"Germline variants in targeted tumor sequencing using matched normal DNA","volume":"2","author":"Schrader","year":"2016","journal-title":"JAMA Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s40779-025-00654-8","article-title":"Clonal hematopoiesis of indeterminate potential: A multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases","volume":"12","author":"Zhang","year":"2025","journal-title":"Mil Med Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-111523-023442","article-title":"Clonal hematopoiesis in nonmalignant disease: Functional consequences of mutated immune cells by clonal hematopoiesis in the diseased tissue","volume":"21","author":"Koh","year":"2025","journal-title":"Annu Rev Pathol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0753-7","article-title":"Primary hemophagocytic lymphohistiocytosis in adults: The utility of family surveys in a single-center study from China","volume":"13","author":"Jin","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1460882","article-title":"Functional role of UNC13D in immune diseases and its therapeutic applications","volume":"15","author":"Duong","year":"2024","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109689","article-title":"TACI and endogenous APRIL in B cell maturation","volume":"253","author":"Garcia-Carmona","year":"2023","journal-title":"Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-20-1353","article-title":"LKB1\/STK11 is a tumor suppressor in the progression of myeloproliferative neoplasms","volume":"11","author":"Marinaccio","year":"2021","journal-title":"Cancer Discov"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.13.16244","article-title":"LKB1\/AMPK\/mTOR signaling pathway in hematological Malignancies: From metabolism to cancer cell biology","volume":"10","author":"Green","year":"2011","journal-title":"Cell Cycle"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02608-7","article-title":"Clonal evolution of chronic lymphocytic leukemia to Langerhans cell histiocytosis: A case report","volume":"475","author":"Frauenfeld","year":"2019","journal-title":"Virchows Arch"},{"key":"B37","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-017-0474-3","article-title":"Checkpoint inhibitors in hematological Malignancies","volume":"10","author":"Ok","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-019-0691-1","article-title":"The role of germline mutation profiling in the selection of related donors for haematopoietic stem cell transplantation","volume":"55","author":"Zebisch","year":"2020","journal-title":"Bone Marrow Transplant"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1880348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:45Z","timestamp":1785212805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1880348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1880348"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1880348","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"article-number":"1880348"}}