caa a22 4500 605490848 CHVBK 20210128100507.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10147-015-0837-0 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0837-0 Molecular pathogenesis of multiple myeloma [Elektronische Daten] [Yusuke Furukawa, Jiro Kikuchi] Multiple myeloma (MM), one of the most intractable malignancies, is characterized by the infiltration and growth of plasma cells, the most differentiated cells in the B-cell lineage, in the bone marrow. Despite the introduction of novel therapeutic agents, including proteasome inhibitors and immunomodulatory drugs, the prognosis of patients with MM is still worse than that of most hematological malignancies. A better understanding of the molecular pathogenesis of the disease is essential to achieve any improvement of treatment outcome of MM patients. All MM cases pass through the phase of asymptomatic expansion of clonal plasma cells, referred to as monoclonal gammopathy of undetermined significance (MGUS). It has long been believed that MM evolves linearly from MGUS to terminal phases, such as extramedullary tumors and plasma cell leukemia via the accumulation of novel mutations. However, recent studies using next-generation sequencing have disclosed the complex genomic architecture of the disease. At each step of progression, the acquisition of novel mutations is accompanied by subclonal evolution from reservoir cloneswith branching patterns. Each subclone may carry novel mutations and distinct phenotypes, including drug sensitivity. In addition, minor clones already exist at the MGUS stage, which could expand later in the clinical course, resulting in relapse and/or leukemic conversion. The ultimate goal of treatment is to eradicate all clones, including subclonal populations with distinct biological characteristics. This goal could be achieved by further improving treatment strategies that reflect the genomic landscape of the disease. Japan Society of Clinical Oncology, 2015 Genetic architecture nationallicence Linear clonal evolution nationallicence Branching evolution nationallicence Intra-clonal heterogeneity nationallicence Drug resistance nationallicence Furukawa Yusuke Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut Kikuchi Jiro Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 413-422 1341-9625 20:3<413 2015 20 10147 https://doi.org/10.1007/s10147-015-0837-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0837-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Furukawa Yusuke Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Kikuchi Jiro Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, 329-0498, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 413-422 1341-9625 20:3<413 2015 20 10147