Biology of multiple myeloma [Biologie des multiplen Myeloms]

Background: Normal bone marrow plasma cells (BMPC) and myeloma cells (MMC) depend on growth and survival factors in the bone marrow (BM) microenvironment which are available in a limited number of BM niches. Accumulation of MMCs transforms the BM microenvironment and induces bone defects and increased BM angiogenesis. This is mediated by aberrant factors (in MMC only, e.g. DKK1, HGF) or factors already expressed in BMPC (e.g. BMP6, VEGFA) in a bidirectional interaction. Material and methods: Methods used in the published articles described comprise gene expression profiling, fluorescence in situ hybridization, genome-wide association studies, array comparative genomic hybridization and sequencing. Results: The results show that MMCs have a multitude of chromosomal aberrations and changes of gene expression correlating with the ability to aberrantly produce corresponding factors. The chromosomal high-risk aberrations in therapy requiring myeloma (t(4;14), del17p, 1q21+) and hyperdiploidy (favorable there) are predictors of progression in asymptomatic myeloma, independent of tumor mass. First publications show a clonal heterogeneity of the MMC clone with three patterns of changes over time (temporal tumor types): (i) genetically stable, (ii) linear evolution and (iii) changing clonal dominance (clonal tides). In the latter case, re-exposition with a line of treatment under which disease progression occurred could be useful if a (different) sensitive subclone appeared under another therapy line. © 2014 Springer-Verlag Berlin Heidelberg. Schlüsselwörter: Multiples MyelomPathogenese Mikroumgebung Progression Temporale Tumortypen.