CD15 expression on leukemic cells associates with extramedullary infiltration and adverse outcomes in Acute Myeloid Leukemia

Abstract

Abstract Objectives: We characterized CD15 expression on leukemic cells across newly diagnosed, relapsed/refractory, and extramedullary-infiltrated acute myeloid leukemia (AML), examined its associations with extramedullary disease, relapse, and clinical outcomes, and explored potential underlying mechanisms.Methods: We retrospectively analyzed 298 newly diagnosed AML patients, defining CD15 positivity as ≥ 10% expression on gated leukemic cells via flow cytometry, and evaluated associations between CD15 status, clinical features, and outcomes. Additionally, CD15 expression was measured in leukemic cells in 40 relapsed/refractory AML patients and in cerebrospinal fluid leukemic cells from 3 patients with central nervous system (CNS) infiltration. To preliminarily explore the potential mechanism of CD15 in leukemia invasion, we selected cell lines with significantly different CD15 expression but similar genetic mutation backgrounds, specifically the CD15-negative KG1A and the CD15-strongly positive (≥ 80%) THP1, conducted colony formation, migration, and invasion assays, and tested the impact of CD15 blockade on cell invasiveness using Transwell chambers coated with an anti-CD15 antibody.Results: CD15 positivity was observed in 26.8% (80/298) of newly diagnosed AML patients. Compared with the CD15-negative group, CD15-positive patients showed higher bone marrow blast percentages (69.4% vs 53.25%), peripheral white blood cell counts (25.62 vs 10.64 ×10⁹/L), M5 subtype frequency (47.8% vs 19.2%), KRAS mutation rates (12.5% vs 4.6%), and extramedullary infiltration incidence (17.5% vs 6.9%) (all P < 0.05). Further analysis revealed that CD15 expression levels were significantly negatively correlated with the proportion of NK cells among lymphocytes and their proportion among nucleated cells (r < -0.3, P = 0.04). In terms of prognosis, the relapse rate was higher in the CD15-positive group (65.5% vs 49.4%); Cox multivariate analysis showed that CD15 positivity, age ≥ 60 years, TP53 mutation, FLT3-ITD high allele burden, and -5 chromosomal aberration were all independent risk factors affecting patients' overall survival (OS) (P < 0.05). Dynamic monitoring showed that the CD15 expression level in leukemic cells of 40 relapsed/refractory AML patients was significantly higher than that in the newly diagnosed stage (P < 0.05); all 3 patients with central nervous system infiltration were CD15-positive, with 2 being strongly positive. In vitro, CD15-high THP1 cells exhibited greater proliferation, migration, and invasion than CD15-negative KG1A cells. After treatment with anti-CD15 antibody coating, the migration and invasion abilities of THP1 were significantly decreased (all P < 0.05).Conclusions: CD15 positivity identifies AML patients at increased risk of extramedullary infiltration, relapse, and poor survival. Mechanistically, CD15 may drive disease progression by enhancing leukemic cell proliferation and invasiveness while impairing NK cell-mediated immunity. These findings support CD15 as a potential biomarker for risk stratification and a candidate therapeutic target in AML.