Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma. Issue 4 (July 2016)

• Record Type: Journal Article
• Authors: Manier, Salomon; Kawano, Yawara; Bianchi, Giada; Roccaro, Aldo M.; Ghobrial, Irene M.
• Is Part Of: Current opinion in hematology. Volume 23:Issue 4(2016:Jul.)
• Publication Date: 2016-07
• Subjects: bone marrow microenvironment in multiple myeloma -- genomic alterations in multiple myeloma -- molecular mechanisms of disease progression from monoclonal gammopathy of undetermined significance to multiple myeloma; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1097/MOH.0000000000000259
• Languages: English
• ISSNs: 1065-6251

Abstract

Abstract : Purpose of review: Multiple myeloma is a plasma cell malignancy evolving in the bone marrow and leading to end organ damage such as bone lesions, cytopenias, and kidney failure. This review delineates recent advances in the molecular mechanisms leading to tumor progression in multiple myeloma. Two different aspects enable tumor expansion: cell autonomous through genomic alterations in the tumor clone and noncell autonomous deregulations in the bone marrow tumor microenvironment. These alterations provide the framework for the continuous progression of multiple myeloma from early precursor conditions such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma. Recent findings: In this review, we discuss recent findings in the genomic alterations that occur in the tumor clone such as somatic genomic mutations, copy number variation and chromosomal translocation, and delineate noncell autonomous deregulations in which tumor cells take advantage of a permissive microenvironment to further proliferate. The latter compartment includes interaction with bone marrow stromal cells, osteoblasts, osteoclasts, and immune escape. Summary: Understanding the mechanisms that lead tumor progression from early stages to overt multiple myeloma could guide to more effective therapies and therefore prevent disease progression.