{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:11:25Z","timestamp":1779387085508,"version":"3.53.1"},"reference-count":74,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Among the many complications that can occur in individuals with sickle cell disease (SCD), several studies have suspected an increased risk of cancer. While the effect of SCD on solid tumors remains unclear, multiple studies support a higher incidence of leukemia, especially acute myeloid leukemia (AML). This risk seems to appear in childhood and persist throughout life. Based on these features, should SCD be considered a cancer predisposition syndrome? Here, we explore this question by comparing the characteristics of SCD-associated AML and cancer predisposition syndromes. We show that some features are similar. As in cancer predisposition syndrome, increased cancer risk in SCD appears to be restricted to a defined type of malignancy. SCD-associated AML also has molecular specificities reminiscent of therapy-related AML. Many of the mechanisms contributing to SCD-associated leukemogenesis have been reported in cancer predisposition syndromes, including ineffective erythropoiesis, increased cell renewal, chronic inflammation, and oxidative stress. Nevertheless, SCD presents a unique combination of factors, and their magnitude may greatly vary from one individual to another. Strikingly, the relative risk of cancer in SCD is much lower than most cancer predisposition syndromes and closer to those conferred by common variations. This is a major difference, and indeed, the absolute risk of malignancy in individuals with SCD appears to be low. Moreover, SCD has great clinical variability, and the factors influencing AML risk are unclear. In sum, SCD has many specificities compared to cancer predisposition syndromes that should be considered and investigated. Clinicians should be aware of the increased risk of AML in patients\u2019 management and counseling.<\/jats:p>","DOI":"10.3390\/children13050683","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:46:18Z","timestamp":1779381978000},"page":"683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Should Sickle Cell Disease Be Considered a Cancer Predisposition Syndrome?"],"prefix":"10.3390","volume":"13","author":[{"given":"Elise","family":"Casadessus","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Pastore","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"},{"name":"CHU Sainte-Justine Azrieli Research Center, Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-333X","authenticated-orcid":false,"given":"Thomas","family":"Pincez","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"},{"name":"CHU Sainte-Justine Azrieli Research Center, Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","article-title":"Germline Mutations in Predisposition Genes in Pediatric Cancer","volume":"373","author":"Zhang","year":"2015","journal-title":"N. 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