Background: Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells driven by gain-of-function mutations in genes. Three phenotypic manifestations of MPNs can be distinguished: PV, ET and PMF. JAK2V617F mutation is present in about 90% patients with PV and 55% patients with ET. Increased energy requirement and metabolic reprogramming has been recognized as one of the hallmarks of cancers.Recent work by our group revealed multilevel defects in the hematopoietic microenvironment in JAK2V617F-positive MPNs resulting from molecular and functional deficits. Whether the insufficient stromal support is related to metabolic changes of the bone marrow niche remains unclear.

Aims: This study aims to explore the metabolic alterations of mesenchymal stromal cells in JAK2-mutant MPNs.

Methods: We collected the supernatant of bone marrow aspirate from clinical JAK2-mutantMPN patients and measured the glucose, triglyceride and total cholesterol in the bone marrow. Total RNA was isolated from (mesenchymal stromal cells) MSCs at passage four and used for transcriptomic analyses. And GO analysis, KEGG analysis and GSEA computational assays were carried out.

Results: (1) The level of glucose, triglyceride and total cholesterol is obviously higher in the bone marrow of JAK2-mutantMPN patients. (2)A total of 766 upregulated and 429 downregulated genes were detected in the MSCs of JAK2-mutant MPN patients. (3) GO analysis revealed changes in the gene sets related to sterol biosynthetic process, cholesterol biosynthesis, cholesterol biosynthetic process, sterol metabolic process and organic hydroxy compound metabolic process. (4) KEGG analysis showed a prominent abundance of gene signatures associated with glycolysis/gluconeogenesis and steroid biosynthesis. (5) GSEA confirmed significant enrichment of dysregulated genes involved in organic hydroxyl compound metabolic process and fatty acid metabolic process.

Conclusions: The level of glucose, triglyceride and total cholesterol was upregulated in the bone marrow of JAK2-mutant MPNs, which may be related to the metabolic alterations displayed by MSCs in the microenvironment.

[The level of glucose, triglyceride and total cholesterol is obviously higher in the bone marrow of JAK2-mutant MPN patients.]

[Mesenchymal stromal cells display metabolic alterations in JAK2-mutant MPNs]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/mesenchymal-stromal-cells-display-metabolic-alterations-in-jak2-mutant-myeloproliferative-neoplasms/