Abstract:
:Multiple myeloma is preceded by an asymptomatic phase, comprising monoclonal gammopathy of uncertain significance and smoldering myeloma. Compared to the former, smoldering myeloma has a higher and non-uniform rate of progression to clinical myeloma, reflecting a subset of patients with higher risk. We evaluated the gene expression profile of smoldering myeloma plasma cells among 105 patients enrolled in a prospective observational trial at our institution, with a view to identifying a high-risk signature. Baseline clinical, bone marrow, cytogenetic and radiologic data were evaluated for their potential to predict time to therapy for symptomatic myeloma. A gene signature derived from four genes, at an optimal binary cut-point of 9.28, identified 14 patients (13%) with a 2-year therapy risk of 85.7%. Conversely, a low four-gene score (< 9.28) combined with baseline monoclonal protein < 3 g/dL and albumin ≥ 3.5 g/dL identified 61 patients with low-risk smoldering myeloma with a 5.0% chance of progression at 2 years. The top 40 probe sets showed concordance with indices of chromosome instability. These data demonstrate high discriminatory power of a gene-based assay and suggest a role for dysregulation of mitotic checkpoints in the context of genomic instability as a hallmark of high-risk smoldering myeloma.
journal_name
Haematologicajournal_title
Haematologicaauthors
Khan R,Dhodapkar M,Rosenthal A,Heuck C,Papanikolaou X,Qu P,van Rhee F,Zangari M,Jethava Y,Epstein J,Yaccoby S,Hoering A,Crowley J,Petty N,Bailey C,Morgan G,Barlogie Bdoi
10.3324/haematol.2015.124651subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1214-21issue
9eissn
0390-6078issn
1592-8721pii
haematol.2015.124651journal_volume
100pub_type
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