Analysis of neutrophil gelatinase-associated lipocalin, vascular endothelial growth factor, and soluble receptor for advanced glycation end-products in bone marrow supernatant in hematologic malignancies

Abstract

Background: Inflammation is a known risk factor of cancer development, including inflammation-driven leukemogenesis. Evaluation of inflammation-related cytokines in early diagnosis stages is crucial to understand the development of hematologic malignancy. Our aim was to measure three cytokines- neutrophil gelatinase-associated lipocalin (NGAL), vascular endothelial growth factor (VEGF), and soluble receptor for advanced glycation end-products (sRAGE) in bone marrow (BM) samples from patients diagnosed with hematologic malignancy and compare these measurements with the control. Additionally, we evaluated whether NGAL was significantly associated with sRAGE, VEGF, and several hematological parameters. Methods: BM samples were collected from 73 patients, who were classified into myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), plasma cell neoplasm (PCN) and control groups according to the BM smear and pathology review. An immunoassay, a Luminex assay, and an enzyme-linked immunosorbent assay were used to quantitate NGAL, VEGF, and sRAGE, respectively, while all measurements of NGAL, VEGF and sRAGE were performed on BM supernatants. Data on hematological parameters were collected from medical records. Intergroup comparisons were performed using the Kruskal-Wallis H-test and Pearson Chi-Square test. Single and multiple regression analyses were performed to analyze the relationships among the parameters. Results: The independent factors associated with NGAL were neutrophil counts and VEGF. As for both NGAL and VEGF, the MPN (n = 23) group showed the highest level, while the MDS (n = 12) group showed low levels. NGAL levels in the AML (n = 13) and MDS groups were lower than in the control group (n = 14). The MPN group demonstrated higher VEGF levels than the AML and MDS groups. The MDS group showed lower VEGF levels than the PCN (n = 11) group. No statistical difference between the hematologic malignancy and control groups or among the hematologic malignancy groups was observed for sRAGE levels. Conclusion: NGAL was related to neutrophil count and VEGF. NGAL and VEGF showed similar intergroup patterns, reflecting that NGAL was associated with VEGF.