Association Between B-Cell Marker Expression and RUNX1 Lesions in Acute Myeloid Leukemia, Beyond RUNX1::RUNX1T1 Fusion: Diagnostic Pitfalls with Mixed-Phenotype Acute Leukemia—B/Myeloid

Authors

Giby V George
Malgorzata Kajstura
Audrey N Jajosky
Hong Fang
Fatima Zahra Jelloul
Andrew G Evans
W Richard Burack
John M Bennett
L Jeffrey Medeiros
Wei Wang
Siba El Hussein

Publication Date

4-18-2025

Journal

Cancers

DOI

10.3390/cancers17081354

PMID

40282530

PMCID

PMC12026294

PubMedCentral® Posted Date

4-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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., ≥20% 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 “mixed-lineage-like” 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).

Keywords

AML, RUNX1, RUNX1::RUNX1T1, B-cell expression, flow cytometry analysis, AML-myelodysplasia-related, plasmacytoid dendritic cell differentiation, pDC-AML

Published Open-Access

yes

Recommended Citation

George, Giby V; Kajstura, Malgorzata; Jajosky, Audrey N; et al., "Association Between B-Cell Marker Expression and RUNX1 Lesions in Acute Myeloid Leukemia, Beyond RUNX1::RUNX1T1 Fusion: Diagnostic Pitfalls with Mixed-Phenotype Acute Leukemia—B/Myeloid" (2025). Faculty, Staff and Student Publications. 5111.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5111