Osteopontin and their roles in hematological malignancies: Splice variants on the new avenues

Abstract

Osteopontin (OPN) is a protein expressed in several tissues, including bone marrow, in which it performs distinct roles, such as modulating hematopoietic stem cell niche and bone remodeling. Most data in hematological malignancies (HMs) refers to total OPN (tOPN), comprehending the sum of distinct OPN splicing isoforms (OPN-SI), while reports describing the expression and roles of each OPN-SI are scarce. This review aims to summarize tOPN roles in HMs and provide evidence that OPN-SIs can also modulate specific functions in HMs biology. We summarize that upregulated tOPN can modulate HMs (leukemia, lymphoma and myeloma) progression, inducing cell adhesion, invasion, angiogenesis, cell differentiation and extramedullary and/or central nervous system infiltration. Based on this expression pattern, tOPN has been pointed out as a biomarker in those HMs, thus providing potential targets for therapeutic approaches. Our group found that OPN-SIs are expressed in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines (unpublished data), providing early evidence that OPN-SIs are also expressed in BCP-ALL. Further studies should investigate whether these OPN-SIs can differently modulate HMs biology and their putative application as auxiliary biomarkers for HMs.

Keywords: Hematological malignancies; Leukemia; Lymphoma; Myeloma; Osteopontin; Splicing isoforms.