Novel Insights from Research Practice Pathobiology 2019;86:162–166 RUNX1 Mutations Can Lead to Aberrant Expression of CD79a and PAX5 in Acute Myelogenous Leukemias: A Potential Diagnostic Pitfall Thomas Menter a Pontus Lundberg b Friedel Wenzel a Jan Dirks b Paula Fernandez c Dorothea Friess d Stefan Dirnhofer a Alexandar Tzankov a a Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland; b Department of Hematology, University Hospital Basel, Basel, Switzerland; c Department of Laboratory Medicine, Cantonal Hospital Aarau, Aarau, Switzerland; d Department of Hematology, Cantonal Hospital Olten, Olten, Switzerland Received: August 3, 2018 Accepted after revision: September 10, 2018 Published online: November 5, 2018 Prof. Dr. med. Alexandar Tzankov Institute of Pathology Schönbeinstrasse 40 CH–4031 Basel (Switzerland) E-Mail alexandar.tzankov @usb.ch © 2018 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/pat Established Facts • Acute myelogenous leukemia (AML) with RUNX1-RUNX1T1 fusion frequently aberrantly expresses the B cell antigens CD19, PAX5, and CD79a. This is due to net inactivation of the myeloid master regulator PU.1 by the chimeric RUNX1-RUNX1T1 protein. • AML with the RUNX1 mutation is a provisional AML sub-entity in the WHO 2017 classification. Such mutations are commonly observed in mixed-lineage leukemia (MLL), and in FLT3-ITD and +13 and +21 AML. Novel Insights • RUNX1 mutant AML can aberrantly express the B cell antigens CD79a and/or PAX5, similarly to AML with RUNX1-RUNX1T1 fusion. • CD79a and PAX5 expression combined with myeloperoxidase negativity or mere detectablity in RUNX1 mutant AML is a potential classificatory pitfall that may lead to misclassification of respective cases as acute lymphoblastic leukemia (ALL). • The expression of B cell markers in RUNX1 mutant AML may be linked to deregulation of the myeloid master regulator PU.1, similarly to what is known for AML with RUNX1-RUNX1T1 fusion. DOI: 10.1159/000493688 Keywords RUNX1 · CD79a · PAX5 · Acute myelogenous leukemia · Acute lymphoblastic leukemia Abstract Background: RUNX1 is a crucial transcription factor for he- matological stem cells and well-known for its association with acute lymphoblastic leukemia (ALL) and acute myelog- enous leukemia (AML). Besides the translocation t(8; 21) that leads to the RUNX1-RUNX1T1 fusion, somatic mutations of RUNX1 have been discovered. Methods: Four bone marrow trephine biopsies of patients with CD79a-positive and/or PAX5-positive acute leukemias were investigated by immu- nohistochemistry (IHC), karyotyping, and next-generation sequencing-based genetic analysis. Data were then com- pared to a historical collective of AML (n = 42) and 42 cases of AML newly diagnosed at our institution between June