{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:39:07Z","timestamp":1790757547807,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and\/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.<\/jats:p>","DOI":"10.1182\/blood.2022019425","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T19:55:09Z","timestamp":1679601309000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["The Clinical Picture of the ERCC6L2 Disease - from Bone Marrow Failure to Acute Leukemia"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-4803","authenticated-orcid":false,"given":"Marja","family":"Hakkarainen","sequence":"first","affiliation":[{"name":"Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0415-8679","authenticated-orcid":false,"given":"Ilse","family":"Kaaja","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics \/ Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-688X","authenticated-orcid":false,"given":"Suvi P. M.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics \/ Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Vulliamy","sequence":"additional","affiliation":[{"name":"Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Professor","given":"Inderjeet","family":"Dokal","sequence":"additional","affiliation":[{"name":"Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Soulier","sequence":"additional","affiliation":[{"name":"Hopital Saint-Louis and Universit\u00e9 Paris-Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-0728","authenticated-orcid":false,"given":"Lise","family":"Larcher","sequence":"additional","affiliation":[{"name":"Hopital Saint-Louis and University de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis","family":"Peffault de Latour","sequence":"additional","affiliation":[{"name":"Saint-Louis, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry M","family":"Leblanc","sequence":"additional","affiliation":[{"name":"H\u00f4pital Robert-Debr\u00e9 - APHP, Paris Cedex 19, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-1556","authenticated-orcid":false,"given":"Flore","family":"Sicre de Fontbrune","sequence":"additional","affiliation":[{"name":"Hopital Saint Louis APHP France, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Siitonen","sequence":"additional","affiliation":[{"name":"Oulu University Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Lohi","sequence":"additional","affiliation":[{"name":"Tampere University, Faculty of Medicine and Health Technology, Tampere University Hospital, Tays Cancer Centre, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hellstr\u00f6m-Lindberg","sequence":"additional","affiliation":[{"name":"Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3185-2962","authenticated-orcid":false,"given":"Gisela","family":"Barbany","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-9958","authenticated-orcid":false,"given":"Akiko","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Dana Farber\/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Beier","sequence":"additional","affiliation":[{"name":"University Hospital Aachen, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-8872","authenticated-orcid":false,"given":"Sharon Rosalie","family":"Jackson","sequence":"additional","affiliation":[{"name":"Te Whatu Ora Health New Zealand Counties Manukau, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-7660","authenticated-orcid":false,"given":"Amir","family":"Kuperman","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzipora C.","family":"Falik Zaccai","sequence":"additional","affiliation":[{"name":"Galilee Medical Center, Nahariya, Israel., Nahariya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Tamary","sequence":"additional","affiliation":[{"name":"Schneider Children Medical Center of Israel, Petah Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-0148","authenticated-orcid":false,"given":"Cristina","family":"Mecucci","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Capolsini","sequence":"additional","affiliation":[{"name":"Hospital \"S.Maria della Misericordia\", Perugia, perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9296-2028","authenticated-orcid":false,"given":"Kirsi","family":"Jahnukainen","sequence":"additional","affiliation":[{"name":"University of Helsinki and Helsinki University Hospital, Children's Hospital, and Pediatric Research Center, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urpu","family":"Salmenniemi","sequence":"additional","affiliation":[{"name":"Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, 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