A gene expression based predictor for high risk myeloma treated with intensive therapy and autologous stem cell rescue

Abstract

Myeloma is characterized by a highly variable clinical outcome. Despite the effectiveness of high-dose therapy, 15% of patients relapse within 1 year. We show that these cases also have a significantly shorter post-relapse survival compared to the others (median 14.9 months vs. 40 months, p = 8.03 × 10^{− 14}). There are no effective approaches to define this potentially distinct biological group such that treatment could be altered. In this work a series of uniformly treated patients with myeloma were used to develop a gene expression profiling (GEP)-based signature to identify this high risk clinical behavior. Gene enrichment analyses applied to the top differentially expressed genes showed a significant enrichment of epigenetic regulators as well as “stem cell” myeloma genes. A derived 17-gene signature effectively identifies patients at high risk of early relapse as well as impaired overall survival. Integrative genomic analyses showed that epigenetic mechanisms may play an important role on transcription of these genes.

Keywords::

• Myeloma
• gene expression profiling
• risk
• predictor

Acknowledgements

This work is supported by Myeloma UK; Cancer Research UK; the Bud Flanagan Leukaemia Fund; and The Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital.

Potential conflict of interest:

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Supplementary material available online

Tables and figures showing further results