{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:23:18Z","timestamp":1787300598137,"version":"build-2736575974"},"reference-count":51,"publisher":"AOSIS","issue":"1","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Background:\u00a0In patients with acute myeloid leukaemia (AML), pathogenic variants in the\u00a0additional sex combs-like 1\u00a0(ASXL1) gene confer poor prognosis and are frequently involved in clonal haematopoiesis of indeterminate potential, with increasing prevalence with advancing age.\nObjective:\u00a0We determined the prevalence of\u00a0ASXL1\u00a0variants in an AML cohort and general elderly population in central South Africa.\nMethods:\u00a0The study included 40 participants with de novo AML and 100 elderly participants (\u2265 65 years). Polymerase chain reactions and Oxford nanopore sequencing of\u00a0ASXL1\u00a0exon 12 were performed on all samples between 01 October 2023 and 30 September 2024.\nResults:\u00a0Of the 40 AML participants, 25 (62.5%) were women, with a median age of 42 years.\u00a0ASXL1\u00a0mutations were detected in 5%. In total, 248\u00a0ASXL1\u00a0variants were detected in 68 of the 100 elderly participants aged 65\u201388 years (mean 71 years). Variants in the coding regions included synonymous (58.4%) and missense (41.6%) variants. Benign variants were detec<\/jats:p>","DOI":"10.4102\/ajlm.v15i1.3061","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:28:28Z","timestamp":1787297308000},"update-policy":"https:\/\/doi.org\/10.4102\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Additional sex combs-like 1 variants in an acute myeloid leukaemia and a general elderly cohort in central South Africa"],"prefix":"10.4102","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-3463","authenticated-orcid":false,"given":"Melissa V.","family":"Bergman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009xwd568","id-type":"ROR","asserted-by":"publisher"}],"name":"University of the Free State"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8148-1242","authenticated-orcid":false,"given":"Jean F.","family":"Kloppers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009xwd568","id-type":"ROR","asserted-by":"publisher"}],"name":"University of the Free State"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5795-5313","authenticated-orcid":false,"given":"Phillip A.","family":"Bester","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009xwd568","id-type":"ROR","asserted-by":"publisher"}],"name":"University of the Free State"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6569-4061","authenticated-orcid":false,"given":"Anne-Cecilia","family":"van Marle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2580","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref0","unstructured":"Vakiti A, Reynolds SB, Mewawalla P. Acute myeloid leukemia [homepage on the Internet]. Treasure Island, FL: StatPearls Publishing; 2024 [cited 2025 Sep 03]. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK507875\/"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev. 2019;36:70\u201387. https:\/\/doi.org\/10.1016\/j.blre.2019.04.005","DOI":"10.1016\/j.blre.2019.04.005"},{"key":"ref2","unstructured":"National Cancer Institute, USA. Surveillance, Epidemiology and End Results (SEER) program. Cancer stat facts: Leukemia \u2013 Acute myeloid leukaemia (AML) [homepage on the Internet]. 2023 [cited 2025 Sep 03]. Available from: https:\/\/seer.cancer.gov\/statfacts\/html\/amyl.html"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Hodkinson KE, Willem P, Moodley M, et al. The genetic landscape of acute myeloid leukaemia in the South African public sector. S Afr J Oncol. 2024;8:a309. https:\/\/doi.org\/10.4102\/sajo.v8i0.309","DOI":"10.4102\/sajo.v8i0.309"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(3):502\u2013526. https:\/\/doi.org\/10.1002\/ajh.26822","DOI":"10.1002\/ajh.26822"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Kansal R. Acute myeloid leukemia in the era of precision medicine: Recent advances in diagnostic classification and risk stratification. Cancer Biol Med. 2016;13(1):41\u201354. https:\/\/doi.org\/10.28092\/j.issn.2095-3941.2016.0001","DOI":"10.20892\/j.issn.2095-3941.2016.0001"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Patel JP, G\u00f6nen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079\u20131089. https:\/\/doi.org\/10.1056\/NEJMoa1112304","DOI":"10.1056\/NEJMoa1112304"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"D\u00f6hner K, Paschka P. Intermediate-risk acute myeloid leukemia therapy: Current and future. Hematology Am Soc Hematol Educ Program. 2014;2014(1):34\u201343. https:\/\/doi.org\/10.1182\/asheducation-2014.1.34","DOI":"10.1182\/asheducation-2014.1.34"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Marando L, Huntly BJP. Molecular landscape of acute myeloid leukemia: Prognostic and therapeutic implications. Curr Oncol Rep. 2020;22(6):61. https:\/\/doi.org\/10.1007\/s11912-020-00918-7","DOI":"10.1007\/s11912-020-00918-7"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: Myeloid and histiocytic\/dendritic neoplasms. Leukemia. 2022;36(7):1703\u20131719. https:\/\/doi.org\/10.1038\/s41375-022-01613-1","DOI":"10.1038\/s41375-022-01613-1"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"D\u00f6hner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345\u20131377. https:\/\/doi.org\/10.1182\/blood.2022016867","DOI":"10.1182\/blood.2022016867"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Asada S, Fujino T, Goyama S, Kitamura T. The role of ASXL1 in hematopoiesis and myeloid malignancies. Cell Mol Life Sci. 2019;76(13):2511\u20132523. https:\/\/doi.org\/10.1007\/s00018-019-03084-7","DOI":"10.1007\/s00018-019-03084-7"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Zhang P, Xu M, Yang F-C. The role of ASXL1\/2 and their associated proteins in malignant hematopoiesis. Curr Stem Cell Rep. 2020;6(1):6\u201315. https:\/\/doi.org\/10.1007\/s40778-020-00168-0","DOI":"10.1007\/s40778-020-00168-0"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Gelsi-Boyer V, Trouplin V, Ad\u00e9la\u00efde J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145(6):788\u2013800. https:\/\/doi.org\/10.1111\/j.1365-2141.2009.07697.x","DOI":"10.1111\/j.1365-2141.2009.07697.x"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci MJ, Birnbaum D. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol. 2012;5:12. https:\/\/doi.org\/10.1186\/1756-8722-5-12","DOI":"10.1186\/1756-8722-5-12"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Fujino T, Kitamura T. ASXL1 mutation in clonal hematopoiesis. Exp Hematol. 2020;83:74\u201384. https:\/\/doi.org\/10.1016\/j.exphem.2020.01.002","DOI":"10.1016\/j.exphem.2020.01.002"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Kakosaiou K, Panitsas F, Daraki A, et al. ASXL1 mutations in AML are associated with specific clinical and cytogenetic characteristics. Leuk Lymphoma. 20183;59(10):2439\u20132446. https:\/\/doi.org\/10.1080\/10428194.2018.1433298","DOI":"10.1080\/10428194.2018.1433298"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"El Nahass Y, Nader H, Sabet S, et al. High frequency of ASXL1 and IDH mutations in young acute myeloid leukemia Egyptian patients. Asian Pac J Cancer Prev. 2022;23(3):977\u2013984. https:\/\/doi.org\/10.31557\/APJCP.2022.23.3.977","DOI":"10.31557\/APJCP.2022.23.3.977"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Yang L, Wei X, Gong Y. Prognosis and risk factors for ASXL1 mutations in patients with newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Cancer Med. 2024;13(1):e6871. https:\/\/doi.org\/10.1002\/cam4.6871","DOI":"10.1002\/cam4.6871"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Chou WC, Huang HH, Hou HA, et al. Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood. 2010;116(20):4086\u20134094. https:\/\/doi.org\/10.1182\/blood-2010-05-283291","DOI":"10.1182\/blood-2010-05-283291"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Schnittger S, Eder C, Jeromin S, et al. ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome. Leukemia. 2013;27(1):82\u201391. https:\/\/doi.org\/10.1038\/leu.2012.262","DOI":"10.1038\/leu.2012.262"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Lipilkin PV, Kulaeva ED, Mashkina EV. Prognostic value of ASXL1 mutations in acute myeloid leukemia: A meta-analysis. Leuk Res. 2022;120:106910. https:\/\/doi.org\/10.1016\/j.leukres.2022.106910","DOI":"10.1016\/j.leukres.2022.106910"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9\u201316. https:\/\/doi.org\/10.1182\/blood-2015-03-631747","DOI":"10.1182\/blood-2015-03-631747"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Medina EA, Delma CR, Yang FC. ASXL1\/2 mutations and myeloid malignancies. J Hematol Oncol. 2022;15(1):127. https:\/\/doi.org\/10.1186\/s13045-022-01336-x","DOI":"10.1186\/s13045-022-01336-x"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Wang K, Zhang W, Yi L, et al. The impact of age and number of mutations on the size of clonal hematopoiesis. Proc Natl Acad Sci USA. 2024;121(8):e2319364121. https:\/\/doi.org\/10.1073\/pnas.2319364121","DOI":"10.1073\/pnas.2319364121"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood. 2013;121(18):3563\u20133572. https:\/\/doi.org\/10.1182\/blood-2013-01-451781","DOI":"10.1182\/blood-2013-01-451781"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Jaiswal S, Natarajan P, Silver AJ, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111\u2013121. https:\/\/doi.org\/10.1056\/NEJMoa1701719","DOI":"10.1056\/NEJMoa1701719"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616\u20133627. https:\/\/doi.org\/10.1182\/blood-2013-08-518886","DOI":"10.1182\/blood-2013-08-518886"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Singh LS, Iqbal G, Singh A, Limbola M, Kumar AV. The impact of next-generation sequencing on biotechnology: A review of current applications. J Sci Res Rep. 2024;30(11):91\u201397. https:\/\/doi.org\/10.9734\/jsrr\/2024\/v30i112536","DOI":"10.9734\/jsrr\/2024\/v30i112536"},{"key":"ref29","unstructured":"Oxford Nanopore Technologies. Platform solution [homepage on the Internet]. 2022 [cited 2025 Sep 03]. Available from: https:\/\/nanoporetech.com"},{"key":"ref30","unstructured":"EMBL-EBI. EMBOSS Needle Pairwise Sequence Alignment (PSA) [homepage on the Internet]. 2024 [cited 2025 Sep 03]. Available from: https:\/\/www.ebi.ac.uk\/jdispatcher\/psa\/emboss_needle"},{"key":"ref31","unstructured":"HGVS Variant Nomenclature Committee (HVNC). HGVS Variant Nomenclature Committee (HVNC) [homepage on the Internet]. 2026 [cited 2025 Sep 03]. Available from: https:\/\/hgvs-nomenclature.org\/stable\/hvnc\/"},{"key":"ref32","unstructured":"The Human Genomics Community. Varsome: The human genomic variant search engine [homepage on the Internet]. 2024 [cited 2025 Sep 03]. Available from: https:\/\/varsome.com"},{"key":"ref33","unstructured":"National Center for Biotechnology Information. ClinVar [homepage on the Internet]. 2025 [cited 2025 Sep 03]. Available from: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/search\/?gene=ASXL1&assembly=GRCh38"},{"key":"ref34","unstructured":"Wellcome Sanger Institute. Catalogue of somatic mutations in cancer [homepage on the Internet]. 2026 [cited 2025 Sep 03]. Available from: https:\/\/www.sanger.ac.uk\/group\/cosmic-catalogue-of-somatic-mutations-in-cancer\/"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30","DOI":"10.1038\/gim.2015.30"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Paschka P, Schlenk RF, Gaidzik VI, et al. ASXL1 mutations in younger adult patients with acute myeloid leukemia: A study by the German-Austrian Acute Myeloid Leukemia Study Group. Haematologica. 2015;100(3):324\u2013330. https:\/\/doi.org\/10.3324\/haematol.2014.114157","DOI":"10.3324\/haematol.2014.114157"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Metzeler KH, Becker H, Maharry K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011;118(26):6920\u20136929. https:\/\/doi.org\/10.1182\/blood-2011-08-368225","DOI":"10.1182\/blood-2011-08-368225"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Pratcorona M, Abbas S, Sanders MA, et al. Acquired mutations in ASXL1 in acute myeloid leukemia: Prevalence and prognostic value. Haematologica. 2012;97(3):388\u2013392. https:\/\/doi.org\/10.3324\/haematol.2011.051532","DOI":"10.3324\/haematol.2011.051532"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Vaughan J, Hodkinson K. Acute myeloid leukaemia in the Johannesburg public sector: A laboratory-based study. S Afr J Oncol. 2024;8:a283. https:\/\/doi.org\/10.4102\/sajo.v8i0.283","DOI":"10.4102\/sajo.v8i0.283"},{"key":"ref40","unstructured":"Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues: International Agency for Research on Cancer. rev. 4th ed. Lyon: IARC Publications; 2017."},{"key":"ref41","unstructured":"Lagunas-Rangel FA, Ch\u00e1vez-Valencia V, G\u00f3mez-Guijosa M\u00c1, Cortes-Penagos C. Acute myeloid leukemia \u2013 Genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res [serial online]. 2017 [cited 2025 Sep 03];11(4):328\u2013339. Available from: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC5767295\/"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Fan Y, Liao L, Liu Y, et al. Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia. Cancer Cell Int. 2021;21(1):526. https:\/\/doi.org\/10.1186\/s12935-021-02233-y","DOI":"10.1186\/s12935-021-02233-y"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Zhu L, Chen R, Li X, et al. The favorable prognostic value of the loss of sex chromosomes in patients with t(8;21) acute myeloid leukemia: An exploratory study. Hematology. 2022;27(1):420\u2013425. https:\/\/doi.org\/10.1080\/16078454.2022.2056982","DOI":"10.1080\/16078454.2022.2056982"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Zhou W, Chen G, Gong D, et al. Loss of the Y chromosome predicts a high relapse risk in younger adult male patients with t(8;21) acute myeloid leukemia on high-dose cytarabine consolidation therapy: A retrospective multicenter study. Leuk Lymphoma. 2020;61(4):820\u2013830. https:\/\/doi.org\/10.1080\/10428194.2019.1683734","DOI":"10.1080\/10428194.2019.1683734"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Ouseph MM, Hasserjian RP, Dal Cin P, et al. Genomic alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells. Haematologica. 2020;106(2):555\u2013564. https:\/\/doi.org\/10.3324\/haematol.2019.240689","DOI":"10.3324\/haematol.2019.240689"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488\u20132498. https:\/\/doi.org\/10.1056\/NEJMoa1408617","DOI":"10.1056\/NEJMoa1408617"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Bou Zerdan M, Nasr L, Saba L, et al. A synopsis clonal hematopoiesis of indeterminate potential in hematology. Cancers (Basel). 2022;14(15):3663. https:\/\/doi.org\/10.3390\/cancers14153663.","DOI":"10.3390\/cancers14153663"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Jongen-Lavrencic M, Grob T, Hanekamp D, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378(13):1189\u20131199. https:\/\/doi.org\/10.1056\/NEJMoa1716863","DOI":"10.1056\/NEJMoa1716863"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Erali M, Voelkerding KV, Wittwer CT. High resolution melting applications for clinical laboratory medicine. Exp Mol Pathol. 2008;85(1):50\u201358. https:\/\/doi.org\/10.1016\/j.yexmp.2008.03.012","DOI":"10.1016\/j.yexmp.2008.03.012"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Bodian DL, McCutcheon JN, Kothiyal P, et al. Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: Implications for individual genome sequencing. PLoS One. 2014;9(4):e94554. https:\/\/doi.org\/10.1371\/journal.pone.0094554","DOI":"10.1371\/journal.pone.0094554"}],"container-title":["African Journal of Laboratory Medicine"],"original-title":[],"link":[{"URL":"https:\/\/ajlmonline.org\/index.php\/ajlm\/article\/view\/3061\/3644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:28:39Z","timestamp":1787297319000},"score":1,"resource":{"primary":{"URL":"https:\/\/ajlmonline.org\/index.php\/ajlm\/article\/view\/3061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.4102\/ajlm.v15i1.3061","relation":{},"ISSN":["2225-2002","2225-2010"],"issn-type":[{"value":"2225-2002","type":"print"},{"value":"2225-2010","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"article-number":"a3061"}}