Integrated transcriptome-proteome analysis in patients with myelofibrosis-related anemia

Objective. Myelofibrosis (MF) represents a hallmark of the advanced stage of myeloproliferative neoplasms (MPNs), and anemia serves as an independent factor for poor prognosis. Our study aimed to explore the gene and protein profile in patients with MF-related anemia through integrated transcriptome-proteome analysis. Methods. Peripheral blood was collected from 36 MPN patients, including 24 anemic individuals. Isolated mononuclear cells were analyzed for differentially expressed genes (DEGs) via transcriptomic sequencing. Plasma samples was tested for differentially expressed proteins (DEPs) using Olink proteomics technology. Potential diagnostic biomarkers for MF-related anemia were identified though combined Lasso regression, logistic regression analysis, and receiver-operating characteristic curve. Results. Gene set enrichment analysis showed that the JAK-STAT signaling pathway is generally downregulated in anemic patients, and DEGs associated with erythroid differentiation were significantly upregulated in the anemia group. Proteomics analysis indicated that TRAIL and CXCL13 were the most significantly downregulated and upregulated DEPs in anemic patients, respectively. Univariate logistic regression analysis suggested positive correlation between IL-6, IL-10, and PD-L1 with anemia, while only IL-10 remained statistically significant in multivariate analysis. ELISA assay confirmed significantly elevated plasma IL-10 levels in patients with MF-related anemia. Conclusions. DEGs associated with erythroid differentiation are highly expressed in anemic patients, confirming the involvement of ineffective erythropoiesis in the pathogenesis of MF-related anemia. Besides abnormally activated inflammatory cytokines, the anti-inflammatory factor IL-10 can also serve as a potential diagnostic biomarker for MF-related anemia, possibly due to a compensatory response arising from reduced sensitivity of monocytes to IL-10.