Can Flow Cytometry Immunophenotyping Predict Cytogenetic Abnormalities in Acute Myeloid Leukemia? A Focus on Myelodysplasia-Related Cytogenetic Abnormalities

Abstract

Introduction: The European LeukemiaNet (ELN) 2022 classification introduced significant modifications to acute myeloid leukemia (AML) categorization, including refined criteria for AML with myelodysplasia-related cytogenetic abnormalities (AML-MRC). While cytogenetic analysis is essential for a definitive diagnosis, the question remains whether flow cytometry can aid in the initial identification of this AML subgroup. This study aimed to characterize the immunophenotypic profiles of AML-MRC and validate previously reported immunophenotypic patterns of AML with t(8;21) and inv(16) using flow cytometry. Methods: This retrospective study analyzed 911 non-acute promyelocytic leukemia (APL) AML cases. Flow cytometric immunophenotyping was performed using a comprehensive panel of 23 markers. Statistical analysis included univariate and multivariate logistic regression to identify discriminatory markers. Results: Among 911 patients, 241 (26.5%) were classified as AML-MRC. AML-MRC patients were significantly older (mean age: 55.9 vs. 47.9 years, p < 0.001) and presented with lower WBC counts (median: 8.9 vs. 24.2 × 10^9/L, p < 0.001) compared to non-MRC cases. AML-MRC demonstrated higher expression of CD34 (75.9% vs. 57.6%, p < 0.001), CD41a (10.8% vs. 4.5%, p = 0.002) and CD235a (5.8% vs. 1.2%, p < 0.001), with CD235a showing the highest discriminatory power (OR 4.458, 95% CI 1.720–11.552). For core-binding factor AML, AML with t(8;21) exhibited characteristic expression of CD19 (46.3% vs. 9.4%, p < 0.001) and CD56 (72.5% vs. 34.5%, p < 0.001), while AML with inv(16) showed distinctive CD34 (88.9% vs. 61.7%, p = 0.004) and CD14 (59.3% vs. 18.1%, p < 0.001) expression patterns. Conclusion: This study identifies markers that distinguish AML-MRC, including CD235a, CD41a, and CD34. This suggests that acute erythroid leukemia and acute megakaryocytic leukemia are subsets within the AML-MRC category. Additionally, the study validates previously reported immunophenotypic characteristics of AML with t(8;21) and inv(16).