Abstract
ABSTRACTAcute leukemias (ALs) are complex hematological disorders, and accurate diagnosis is crucial for guiding treatment decisions and predicting patient outcomes. While changes in cell marker levels are well documented, the impact of these changes on marker relationships through an integrative systems approach remains uncharacterized. To address this gap, we conducted a 12-year study investigating 41 markers, including ontogenic markers and those used to diagnose both common and rare leukemia types, using immunophenotyping flow cytometry (IFC) data from 1,069 leukocyte samples obtained from peripheral blood (PB) or bone marrow (BM) aspirates of patients with suspected ALs. Machine learning techniques, such as principal component analysis (PCA) and random forest (RF) classification, demonstrated the stratification power of the cellular markers. Hierarchical clustering analysis of leukocyte ontogenetic markers revealed disease-specific clusters, irrespective of sex or sample type (PB or BM). Additionally, we found that patients with acute myeloid leukemia (AML) showed mild disruption in cell marker correlations, whereas the most significant dysregulation was observed in patients with T-cell acute lymphoblastic leukemia (T-ALL). Importantly, we identified ontogenic correlation changes indicating clusters of immature versus mature leukocyte markers, as well as cell lineage-specific markers influencing cellular relationships. These findings underscore the value of integrating systems strategies into conventional IFC analyses to enhance synthetic diagnosis and deepen our understanding of ALs pathophysiology.
Publisher
Cold Spring Harbor Laboratory