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The molecular characterization and clinical management of multiple myeloma in the post-genome era

Leukemia volume 23, pages 1941–1956 (2009)Cite this article

Abstract

Cancer-causing mutations disrupt coordinated, precise programs of gene expression that govern cell growth and differentiation. Microarray-based gene-expression profiling (GEP) is a powerful tool to globally analyze these changes to study cancer biology and clinical behavior. Despite overwhelming genomic chaos in multiple myeloma (MM), expression patterns within tumor samples are remarkably stable and reproducible. Unique expression patterns associated with recurrent chromosomal translocations and ploidy changes defined molecular classes with differing clinical features and outcomes. Combined molecular techniques also dissected two distinct, reproducible forms of hyperdiploid disease and have molecularly defined MM with high risk for poor clinical outcome. GEP is now used to risk-stratify patients with newly diagnosed MM. Groups with high-risk features are evident in all GEP-defined MM classes, and GEP studies of serial samples showed that risk increases over time, with relapsed disease showing dramatic GEP shifts toward a signature of poor outcomes. This suggests a common mechanism of disease evolution and potentially reflects preferential expansion of therapy-resistant cells. Correlating GEP-defined disease class and risk with outcomes of therapeutic regimens reveals class–specific benefits for individual agents, as well as mechanistic insights into drug sensitivity and resistance. Here, we review modern genomics contributions to understanding MM pathogenesis, prognosis, and therapy.

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Acknowledgements

This work was supported by the National Cancer Institute (grants CA55819-09 and CA97513-01), the Lebow Fund to Cure Myeloma, and the Nancy and Stephen Grand Fund. The manuscript was edited by the Office of Grants and Scientific Publications, University of Arkansas for Medical Sciences.

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Authors and Affiliations

  1. Donna D and Donald M Lambert Laboratory for Myeloma Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Y Zhou, B Barlogie & J D Shaughnessy Jr

  2. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Y Zhou, B Barlogie & J D Shaughnessy Jr

  3. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    J D Shaughnessy Jr

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  1. Y Zhou
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  2. B Barlogie
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  3. J D Shaughnessy Jr
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Correspondence to J D Shaughnessy Jr.

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Zhou, Y., Barlogie, B. & Shaughnessy, J. The molecular characterization and clinical management of multiple myeloma in the post-genome era. Leukemia 23, 1941–1956 (2009). https://doi.org/10.1038/leu.2009.160

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  • DOI: https://doi.org/10.1038/leu.2009.160

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