4.7 Article

Minor clone provides a reservoir for relapse in multiple myeloma

期刊

LEUKEMIA
卷 27, 期 2, 页码 473-481

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2012.226

关键词

multiple myeloma; genomic analysis; nonlinear evolution

资金

  1. IFM
  2. French National Research Agency [R08079NS]
  3. French Institute National du Cancer [R09076NN]
  4. National Institutes of Health [PO1 CA155258-01, RO1-124929, P50-100007, PO1-78378]
  5. Department of Veterans Affairs Merit Review Awards

向作者/读者索取更多资源

Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-kappa B-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission. Leukemia (2013) 27, 473-481; doi:10.1038/leu.2012.226

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