Analysis of the Relationship between the Expression Levels of Neutrophil Gelatinase-Associated Lipocalin and Cytokine Genes in Bone Marrow.

ABSTRACT

Background: Recently, various associations of NGAL with several hematological cancers have been reported. However, given that the regulation of NGAL gene expression by cytokines is tissue-specific, NGAL expression in relation to those of cytokine genes has not been analyzed in bone marrow (BM) tissue. The purpose of this study was to analyze the association between NGAL and 48 cytokine gene expression levels in mononuclear cells (MNCs) of BM at the time of diagnosis of hematological malignancy and to explore the expression pattern of NGAL and related cytokine genes in patients with hematological malignancies and controls. Methods: BM MNCs were isolated from 48 patients, who were classified as patients presenting myeloproliferative neoplasm, acute myeloid leukemia, myelodysplastic syndrome, and as controls. NGAL and cytokine genes were analyzed using NanoString. Data on hematological parameters were collected from medical records. Single and multiple regression analyses were performed to analyze relationships. Results: Normalized counts of 26 cytokine genes were related to NGAL normalized counts, while STAT3 and TLR4 normalized counts had the highest explanatory power. The following multiple regression model was developed NGAL normalized counts=4316.825 + 9.056 × STAT3 normalized counts + 844.226 × IL5 normalized counts + 17.540 × TLR1 normalized counts - 28.206 × TLR2 normalized counts - 42.524 × IRAK4 normalized counts. In the multiple regression analysis, STAT3 and TLR4 normalized counts showed multicollinearity. NGAL, STAT3, IL5, and TLR4 normalized counts showed similar intergroup patterns. Conclusions: NGAL normalized counts was predicted by a multiple regression model, while they showed similar intergroup patterns to STAT3, IL5, and TLR4 normalized counts.