Myelodysplastic syndromes (MDS) are preleukemic disorders characterized by clonal growth of mutant hematopoietic stem and progenitor cells. MDS are associated with proinflammatory signaling, dysregulated immune response, and cell death in the bone marrow (BM). Aging, autoinflammation and autoimmunity are crucial features of disease progression, concordant with promoting growth of malignant clones and accumulation of mutations. Suprabasin (SBSN), a recently proposed proto-oncogene of unknown function, physiologically expressed in stratified epithelia, is associated with poor prognosis of several human malignancies. Here, we showed that SBSN is expressed in the BM by myeloid cell subpopulations, including myeloid-derived suppressor cells, and is secreted into BM plasma and peripheral blood of MDS patients. The highest expression of SBSN was present in a patient group with poor prognosis. SBSN levels in the BM correlated positively with blast percentage and negatively with CCL2 chemokine levels and lymphocyte count. In vitro treatment of leukemic cells with interferon-gamma and demethylating agent 5-azacytidine (5-AC) induced SBSN expression. This indicated that aberrant cytokine levels in the BM and epigenetic landscape modifications in MDS patients may underlie ectopic expression of SBSN. Our findings suggest SBSN as a candidate biomarker of high-risk MDS with a possible role in disease progression and therapy resistance.

• Keywords
• 5-azacytidine, MDS, MDSCs, biomarker, suprabasin,
• MeSH
• Azacitidine pharmacology   MeSH
• Biomarkers blood   metabolism   MeSH
• Chemokine CCL2 metabolism   MeSH
• Antigens, Differentiation blood   genetics   metabolism   MeSH
• HEK293 Cells MeSH
• Interferon-gamma pharmacology   MeSH
• Cell Compartmentation drug effects   MeSH
• Bone Marrow metabolism   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Myelodysplastic Syndromes blood   metabolism   MeSH
• Myeloid Cells drug effects   metabolism   MeSH
• Cell Line, Tumor MeSH
• Neoplasm Proteins blood   genetics   metabolism   MeSH
• Lymphocyte Count MeSH
• Prognosis MeSH
• Proto-Oncogene Mas MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Azacitidine MeSH
• Biomarkers MeSH
• Chemokine CCL2 MeSH
• Antigens, Differentiation MeSH
• Interferon-gamma MeSH
• MAS1 protein, human MeSH Browser
• RNA, Messenger MeSH
• Neoplasm Proteins MeSH
• Proto-Oncogene Mas MeSH
• SBSN protein, human MeSH Browser