Overexpression of annexin A5 might guide the gemtuzumab ozogamicin treatment choice in patients with pediatric acute myeloid leukemia

Abstract

Background: Acute myeloid leukemia (AML) is a common hematological malignancy. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 antibody conjugated with the potent anti-tumor antibiotic calicheamicin, represents a promising targeted therapy for AML. Annexin A5 (ANXA5) is a proposed marker for the clinical prognosis of AML to guide treatment choice. Methods: In total, 253 patients with pediatric AML were enrolled and divided into two treatment groups: conventional chemotherapy alone and conventional chemotherapy in combination with GO. Univariate, multivariate, and Kaplan–Meier survival analyses were conducted to assess risk factors and clinical outcomes, and to estimate hazard ratios (HRs) and their 95% confidence interval. The level of statistical significance was set at p < 0.05. Results: In the GO treatment group, high ANXA5 expression was considered a favorable prognostic factor for overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that high ANXA5 expression was an independent favorable factor for OS (HR = 0.629, p = 0.084) and EFS (HR = 0.544, p = 0.024) distinct from the curative effect of GO treatment. When all patients were again divided into two groups, this time based on the median expression of ANXA5, patients undergoing chemotherapy combined with GO had significantly better OS ( p = 0.0012) and EFS ( p = 0.0003) in the ANXA5 high-expression group. Gene set enrichment analysis identified a relevant series of pathways associated with glutathione metabolism, leukocyte transendothelial migration, and hematopoietic cell lineage. Conclusion: The expression level of ANXA5 can help optimize the treatment regimen for individual patients, and patients with overexpression of ANXA5 may circumvent poor outcomes from chemotherapy combined with GO.