A translational perspective of the malignant hematopoietic proteoglycome

Proteoglycans are an ample family of complex extracellular matrix/cell surface components known to impact on virtually all biological processes that take place during life of a human being, in its healthy and diseased conditions. They are consolidated multivalent regulators of the behaviour of normal and malignant hematopoietic cells because of being critical components of their membranes, because of their pivotal role as multifaceted factors of the hematopoietic niches and because of acting as pillars of the tumour microenvironment. Likewise, they act as promoters of the growth, spreading and therapeutic resistance of diseased hematopoietic cells, also by modulating intracellular processes through a dual utilization of core protein domains and their glycosaminoglycan side chains. The intricate pattern of expression of the myriads of proteoglycan isoforms generated by differential glycanations of the core proteins is differentiation- and cell activation-dependent and often associates with genomic aberrations and gene amplifications. Selected proteoglycans stand out as widely recognized, disease type-specific markers and as alluring but still unappreciated therapeutic targets. We therefore pose here a clinical-translational view on the hematopoietic proteoglycome to highlight its underestimated biological and pathological significance during normal and neoplastic hematopoiesis. We underscore the potential of several proteoglycans to be exploited as key markers for prognostication and therapeutic targeting of hematopoietic cancers.