Study on the correlation between bone marrow adipocytokines and myelodysplastic syndromes

Abstract

Objective: To explore the relationship between adipocytokine levels in bone marrow and the onset, progression, and prognosis of myelodysplastic syndromes (MDS). Methods: Retrospective analysis of adipocytokine levels in the bone marrow of 72 patients with MDS and 16 patients with MDS-related secondary acute myeloid leukemia (sAML), including adiponectin (ADP), leptin (LEP), visfatin/nicotinamide phosphoribosyltransferase (NAMPT), adipsin/complement factor D (CFD), and C1q/TNF-related protein 1 (CTRP1), detected by enzyme-linked immunosorbent assay (ELISA) at The Affiliated Cancer Hospital of Zhengzhou University from February 2020 to February 2022. High-throughput sequencing was used to detect MDS-related genes in 70 patients and the relationship between adipocytokines and the clinical characteristics, disease subtypes, mutant genes, and prognosis of patients were analyzed. Seventy-eight MDS-related genes were identified. Results: Clinical characteristics showed that ADP (P=0.027) and LEP (P=0.019) levels were significantly lower in men than inwomen; ADP (P=0.020), CFD (P<0.001), and NAMPT (P=0.021) levels were significantly lower in patients aged <65 years than in patients aged ≥65, whereas LEP levels were significantly higher (P=0.043). Adiponectin levels were significantly higher in patients with BMI<24 than in patients with BMI≥24 (P=0.025), whereas LEP levels were significantly lower (P=0.020); NAMPT levels were significantly higher in the group with increased blasts than in the group with no blasts (P=0.037).The CTRP1 levels were significantly higher in the MDS group than in the sAML group (P=0.010). Abnormal gene correlation analysis showed that elevated CTRP1 levels were positively correlated with the occurrence of epigenetically related abnormal genes (P=0.001) and were positively correlated with the occurrence of TET2 and U2AF1 (P<0.001 and P=0.036, respectively); ADP and CFD levels were positively correlated with the occurrence of NPM1 (P=0.048 and P=0.026, respectively). Multifactorial Cox proportional hazards regression model analysis showed that LEP <0.2 ng/mL was an independent risk factor for progression-free survival (PFS) and overall survival in patients with MDS (P=0.002 and P<0.001, respectively), whereas NAMPT <2.1 ng/mL was a protective factor for PFS in patients with MDS (P=0.043). Conclusions: Adipocytokines in the bone marrow microenvironment are closely associated with the clinical characteristics, gene mutations, and prognosis of patients with MDS, with LEP <0.2 ng/mL being an independent prognostic risk factor and NAMPT <2.1 ng/mL being a prognostic protective factor.