{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T20:05:36Z","timestamp":1748981136132,"version":"3.40.5"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Reduction of blood group ABO antigens on red blood cells (RBCs) is well known in patients with leukemias, and this reduction of <jats:italic>ABO<\/jats:italic> expression is strongly associated with DNA methylation of the <jats:italic>ABO<\/jats:italic> promoter. Previously, we reported a two\u2010nucleotide deletion in <jats:italic>RUNX1<\/jats:italic> encoding an abnormally elongated protein lacking the <jats:italic>trans<\/jats:italic>\u2010activation domain in a patient with myelodysplastic syndrome (MDS) showing A\u2010antigen loss on RBCs. This prompted us to investigate the underlying mechanism responsible for A\u2010antigen reduction on RBCs in another patient with MDS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>Screening of somatic mutations was carried out using a targeted sequencing panel with genomic DNA from peripheral blood mononuclear cells from the patient and eleven MDS controls without A\u2010 or B\u2010antigen loss. DNA methylation of the <jats:italic>ABO<\/jats:italic> promoter was examined by bisulfite genomic sequencing. Transient transfection assays were performed for functional evaluation of mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Screening of somatic mutations showed missense mutations in <jats:italic>RUNX1<\/jats:italic> and <jats:italic>GATA2<\/jats:italic> in the patient, while no mutation was found in exons of those genes in the controls. There was no significant difference in <jats:italic>ABO<\/jats:italic> promoter methylation between the patient and the controls. Transient transfection experiments into COS\u20107 and K562 cells suggested that the amino acid substitutions encoded by those mutations reduced or lost the <jats:italic>trans<\/jats:italic>\u2010activation potential of the <jats:italic>ABO<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Considering the discrepancy between the variant frequencies of these mutations and the ratios of the RBCs with A\u2010antigens loss, the antigen reduction might be associated with these somatic mutations and hypermethylation of the <jats:italic>ABO<\/jats:italic> promoter.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.16766","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T04:09:25Z","timestamp":1639714165000},"page":"469-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reduction of blood group A antigen on erythrocytes in a patient with myelodysplastic syndrome harboring somatic mutations in <i>RUNX1<\/i> and <i>GATA2<\/i>"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-6617","authenticated-orcid":false,"given":"Akira","family":"Hayakawa","sequence":"first","affiliation":[{"name":"Department of Legal Medicine Gunma University Graduate School of Medicine  Maebashi Japan"},{"name":"Department of Oncology\u2010Pathology Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-2699","authenticated-orcid":false,"given":"Rie","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Gunma University Graduate School of Medicine  Maebashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Gunma University Graduate School of Medicine  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