{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:36Z","timestamp":1787027856337,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and\/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B\/myeloid (i.e., \u226520% blasts expressing B and myeloid lineage antigens) in most cases. These findings suggest that AML cases with RUNX1 lesions including mutations, copy number gains, and translocations other than RUNX1T1 fusion, also commonly express B-cell markers, imparting a \u201cmixed-lineage-like\u201d immunophenotype in cases of AML that otherwise fulfill the criteria for other defined subtypes. We present these cases as to caution regarding this potential diagnostic pitfall and favor a diagnosis of AML with RUNX1 lesion(s) in the setting of a case of AML with myeloid\/B-cell antigen expression, a history of myelodysplasia or cytotoxic therapy, the demonstration of pDC differentiation by flow cytometry (generally associated with the presence of a RUNX1 mutation), and the presence of a RUNX1 lesion (mutation, copy number gain, and\/or translocation exclusive of a rearrangement with RUNX1T1).<\/jats:p>","DOI":"10.3390\/cancers17081354","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T23:16:46Z","timestamp":1744931806000},"page":"1354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association Between B-Cell Marker Expression and RUNX1 Lesions in Acute Myeloid Leukemia, Beyond RUNX1::RUNX1T1 Fusion: Diagnostic Pitfalls with Mixed-Phenotype Acute Leukemia\u2014B\/Myeloid"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9529-4564","authenticated-orcid":false,"given":"Giby V.","family":"George","sequence":"first","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Kajstura","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-2496","authenticated-orcid":false,"given":"Audrey N.","family":"Jajosky","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-5959","authenticated-orcid":false,"given":"Hong","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Zahra","family":"Jelloul","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Evans","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-584X","authenticated-orcid":false,"given":"W. Richard","family":"Burack","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-8006","authenticated-orcid":false,"given":"L. Jeffrey","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-7107","authenticated-orcid":false,"given":"Siba","family":"El Hussein","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Vermont Larner College of Medicine, Burlington, VT 05401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1182\/blood-2016-10-687830","article-title":"Role of RUNX1 in hematological malignancies","volume":"129","author":"Sood","year":"2017","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1200\/JCO.2010.30.7926","article-title":"RUNX1 mutations in acute myeloid leukemia: Results from a comprehensive genetic and clinical analysis from the AML study group","volume":"29","author":"Gaidzik","year":"2011","journal-title":"J. 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