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Gene Expression Signature in MGUS and Multiple Myeloma

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Genetic and Molecular Epidemiology of Multiple Myeloma

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Abstract

Despite improvement in therapeutic efficacy, multiple myeloma (MM) remains incurable with a median survival of approximately 10 years. Gene expression profiling (GEP) can be used to elucidate the molecular basis for resistance to chemotherapy through global assessment of molecular alterations that exist at diagnosis, after therapeutic treatment and that evolve during tumor progression. Unique GEP signatures associated with recurrent chromosomal translocations and ploidy changes have defined molecular classes with differing clinical features and outcomes. When compared to other stratification systems, the GEP70 test remained a significant predictor of outcome, reduced the number of patients classified with a poor prognosis, and identified patients at increased risk of relapse despite their standard clinicopathologic and genetic findings. GEP studies of serial samples showed that risk increases over time, with relapsed disease showing GEP shifts toward a signature of poor outcomes. GEP signatures of myeloma cells after therapy were prognostic for event-free and overall survival and thus may be used to identify novel strategies for overcoming drug resistance. This chapter will focus on the use of GEP of MM to define high-risk myeloma and elucidate underlying mechanisms that are beginning to change clinical decision-making and inform drug design.

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Acknowledgements

This work was supported by the Lebow Fund to Cure Myeloma.

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Authors and Affiliations

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

    Christoph J. Heuck M.D. & Qing Zhang Ph.D.

  2. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Sarah K. Johnson Ph.D.

  3. Signal Genetics, LLC, 667 Madison Ave., New York, 10065, USA

    John D. Shaughnessy Jr. Ph.D.

  4. Myeloma Health, LLC, 667 Madison Ave., New York, 10065, USA

    John D. Shaughnessy Jr. Ph.D.

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  1. Christoph J. Heuck M.D.
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  2. Sarah K. Johnson Ph.D.
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  3. Qing Zhang Ph.D.
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  4. John D. Shaughnessy Jr. Ph.D.
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Correspondence to John D. Shaughnessy Jr. Ph.D. .

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  1. College of Physicians and Surgeons, Multiple Myeloma and Amyloidosis Service, Columbia University, 161 Fort Washington Avenue, New York, 10032, New York, USA

    Suzanne Lentzsch

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Heuck, C.J., Johnson, S.K., Zhang, Q., Shaughnessy, J.D. (2013). Gene Expression Signature in MGUS and Multiple Myeloma. In: Lentzsch, S. (eds) Genetic and Molecular Epidemiology of Multiple Myeloma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4660-6_2

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