الفهرس | Only 14 pages are availabe for public view |
Abstract Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cell representing the second most common hematological malignancy. Even though biologics transformed the landscape of MM treatment, cure is still an unmet clinical need. As such, decoding the mechanisms underlying the pathogenesis of MM is critical for development of new therapeutic approaches to treatment and long-term disease remission. Neoplastic transformation in MM is initiated in secondary lymphoid tissue (SLT) germinal center (GC) where B-cell committed to terminal differentiation into plasma cell (PC) but still targeted by on-goin somatic hypermutation (SHM).The neoplastic PCs preferentially home to the bone marrow (BM), where extensive studies substantiated the role of marrow stroma in survival, growth and drug resistance of myeloma cells. The relationship between SLT and BM micro-environments in MM has not been fully elucidated. Nevertheless, it has been recently shown that secreted protein acidic and rich in cysteine (SPARC) is a common stromal motif expressed in micro-environments suggesting a continuous role in MM pathogenesis. We reason that common molecular patterns operate at both sites of the origin (SLTs) and the destination (BM) of the MM disease. One of these molecules, a protein called 2SPARC3 expressed in both micro-environments; we hypothesized that SPARC dysregulation in the GCs and BM stroma promotes Myelomagenesis and that therapeutic rectification of SPARC levels would inhibit MM progression |