Publications (2)4.76 Total impact
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Article: Expression, adverse prognostic significance and therapeutic small molecule inhibition of Polo-like kinase 1 in multiple myeloma.
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ABSTRACT: The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of PLK1 protein in myeloma patient bone marrow biopsies is an independent adverse prognostic factor (HR=2.3, p=0.003 unadjusted; HR=1.9, p=0.03 in multivariable model). BI 2536 inhibits myeloma cell lines at nanomolar concentrations, and is therapeutic for xenografts in NOD/SCID mice. PLK1 inhibition is a potential new strategy for the treatment of multiple myeloma.Leukemia research 08/2011; 35(12):1637-43. · 2.36 Impact Factor -
Article: Expression and prognostic significance of Oct2 and Bob1 in multiple myeloma: implications for targeted therapeutics.
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ABSTRACT: The B/plasma cell transcription factor Oct2 and its co-activator Bob1 activate the immunoglobulin heavy chain (IgH) gene enhancer. IgH translocations occur in the majority of myeloma cases, leading to overexpression of genes juxtaposed to the IgH enhancers. We hypothesized that Oct2 and Bob1 are determinants of disease behavior and potential therapeutic targets in myeloma. Oct2 and Bob1 gene expressions were measured in CD138+ plasma cells and CD138-cells from bone marrow samples from patients with myeloma (n = 37); gene expression of Oct2 and Bob1 was higher in CD138+ than in CD138-cells (p < 0.0001). Oct2 and Bob1 protein expressions were assessed in bone marrow tissue microarrays from patients with myeloma (n = 169) with fluorescent immunohistochemistry, and correlated to patient survival. High Oct2 protein expression correlated with reduced survival (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.11-2.73, p = 0.0164), whereas high Bob1 protein expression correlated with increased survival (HR 0.46, 95% CI 0.29-0.71, p = 0.0008). Oct2 should be explored as a potential selective therapeutic target in myeloma.Leukemia & lymphoma 04/2011; 52(4):659-67. · 2.40 Impact Factor
