{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:53:55Z","timestamp":1787504035993,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,13]],"date-time":"2024-10-13T00:00:00Z","timestamp":1728777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pearson syndrome (PS) and Kearns\u2010Sayre syndrome (KSS) are single large\u2010scale mitochondrial DNA deletion (SLSMD) syndromes. PS is characterized by severe, transient childhood cytopenia, whereas KSS typically manifests later in life without hematologic abnormalities. Despite distinct clinical presentations, both share a common mitochondrial DNA deletion. Recent observations suggest a potential link between PS progression and myeloid malignancy development, indicating that bone marrow failure (BMF) may be a key aspect of PS pathology and potentially universal across SLSMDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study explores longitudinal hematological manifestations of SLSMD syndromes, focusing on bone marrow (BM) dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen patients with SLSMDs (13 PS and 3 KSS) were followed, of whom 75% experienced cytopenia, necessitating blood transfusions in 56%. Despite achieving transfusion independence at a median age of 24 months, persistent hematological abnormalities were noted. Comprehensive longitudinal BM studies were conducted in 62% of subjects and consistently revealed signs of marrow dysfunction, even without concurrent cytopenia. Median BM cellularity at a median age of four years and eight months was 50%, with histological signs of dyserythropoiesis, abnormal megakaryocytes, and signs suggesting myelodysplasia. Reduced CD34\n                      <jats:sup>+<\/jats:sup>\n                      counts and BM colony\u2010forming unit capacity were noted, alongside chromosome 7 aberrations in 16% of patients on cytogenetic studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings establish BM dysfunction as a persistent hallmark of SLSMD syndromes, posing a risk of clonal evolution and acquisition of chromosome 7 aberrations. This aligns with recent literature, emphasizing enduring BMF in SLSMD syndromes and advocating for tailored hematological monitoring guidelines for this unique patient cohort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.31383","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:19:26Z","timestamp":1728865166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long\u2010term hematopoietic dysfunction in patients with large\u2010scale mitochondrial DNA deletion syndromes"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9013-9537","authenticated-orcid":false,"given":"Noa","family":"Greenberg\u2010Kushnir","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology and Oncology The Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel Hashomer Israel"},{"name":"Faculty of Medicinal and Health Sciences Tel Aviv University  Tel Aviv Israel"},{"name":"The Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-8921","authenticated-orcid":false,"given":"Liron D.","family":"Grossmann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology The Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel Hashomer Israel"},{"name":"The Edmond and Lily Safra Children's Hospital Sheba Medical Center  Tel Hashomer Israel"},{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8329-8409","authenticated-orcid":false,"given":"Assaf Arie","family":"Barg","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology The Edmond and Lily Safra Children's Hospital Sheba 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