Proteomics in myelodysplastic syndromes: towards novel prognostic and diagnostic biomarkers.

Myelodysplastic neoplasms (MDS) are clonal hematopoietic disorders defined by ineffective hematopoiesis, cytopenias, and variable risk of progression to acute myeloid leukemia. Although genomic and epigenomic studies have provided insight into disease pathogenesis, reliable biomarkers for diagnosis and prognosis remain limited. Proteomics offers an important advantage because it reflects the functional protein state and captures post-translational modifications, making it highly relevant for risk assessment and therapy guidance. Recent studies have identified several groups of candidate biomarkers. Kinases and signal transduction proteins such as CAMK1D, PRKCZ, KIT, MAST4, PAK6, PTK7, and NTRK1 are dysregulated in MDS and associated with poor outcomes, immune evasion, and aberrant stem cell signaling. Oncofetal proteins like IGF2BP3 and signaling regulators such as RBP4 further highlight proteomic signatures linked to chemoresistance and subtype specificity. In the transplant setting, immune regulators including CSK, FGR, CRTAM, GP1BA, UBE2N, and STAT1 may serve as predictors of graft rejection and relapse. Cytoskeletal and extracellular matrix proteins such as CEP55, Talin-1, Kindlin-3, Vinculin, THBS1, LRG1, SPARC, SAA1, Clusterin, and PRDM16 underscore the role of bone marrow microenvironmental remodeling and adhesion defects in disease progression. Finally, metabolic enzymes such as LDHA reflect altered energy metabolism and correlate with more aggressive disease biology. Collectively, these proteomic candidates illustrate the complex interplay of signaling, immune regulation, bone microenvironment, and metabolism in MDS. Their validation in clinical cohorts could enable early detection, refined risk stratification, and new therapeutic avenues, positioning proteomics as a central tool in the future management of MDS.