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.

1st Department of Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Danish Cancer Society Research Center Copenhagen Denmark

Department of Genome Integrity Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Department of Genomics Institute of Hematology and Blood Transfusion Prague Czech Republic

Division of Genome Biology Department of Medical Biochemistry and Biophysics Science for Life Laboratory Karolinska Institute Stockholm Sweden

Group of Mechanisms Involved in Remodeling of Chromatin Structure During Cell Fate Decisions BIOCEV Prague Czech Republic

Institute of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Molecular Therapy of Cancer Group Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prague Czech Republic

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Suprabasin-A Review