TY - JOUR
T1 - The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition
AU - Chng, Wee J.
AU - Braggio, Esteban
AU - Mulligan, George
AU - Bryant, Barbara
AU - Remstein, Ellen
AU - Valdez, Riccardo
AU - Dogan, Ahmet
AU - Fonseca, Rafael
PY - 2008
Y1 - 2008
N2 - Centrosome amplification is common in myeloma and may be involved in disease pathogenesis. We have previously derived a gene expression-based centrosome index (CI) that correlated with centrosome amplification and was an independent prognostic factor in a small cohort of heterogeneously treated patients. In this study, we validated the prognostic significance of the CI in 2 large cohorts of patients entered into clinical trials and showed that a high CI is a powerful independent prognostic factor in both newly diagnosed and relapsed patients, whether treated by intensive therapy (total therapy II) or novel agents (bortezomib). Tumors with high CI overexpressed genes coding for proteins involved in cell cycle, proliferation, DNA damage, and G2-M checkpoints, and associated with the centrosome and kinetochore/microtubules. In particular, aurora kinases are significantly overexpressed in patients with high CI, with concordant increase in protein expression. Human myeloma cell lines with higher CI are more responsive to treatment with a novel aurora kinase inhibitor. Aurora kinase may represent novel therapeutic targets in these patients with very poor prognosis.
AB - Centrosome amplification is common in myeloma and may be involved in disease pathogenesis. We have previously derived a gene expression-based centrosome index (CI) that correlated with centrosome amplification and was an independent prognostic factor in a small cohort of heterogeneously treated patients. In this study, we validated the prognostic significance of the CI in 2 large cohorts of patients entered into clinical trials and showed that a high CI is a powerful independent prognostic factor in both newly diagnosed and relapsed patients, whether treated by intensive therapy (total therapy II) or novel agents (bortezomib). Tumors with high CI overexpressed genes coding for proteins involved in cell cycle, proliferation, DNA damage, and G2-M checkpoints, and associated with the centrosome and kinetochore/microtubules. In particular, aurora kinases are significantly overexpressed in patients with high CI, with concordant increase in protein expression. Human myeloma cell lines with higher CI are more responsive to treatment with a novel aurora kinase inhibitor. Aurora kinase may represent novel therapeutic targets in these patients with very poor prognosis.
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U2 - 10.1182/blood-2007-06-097774
DO - 10.1182/blood-2007-06-097774
M3 - Article
C2 - 18006703
AN - SCOPUS:38949203768
SN - 0006-4971
VL - 111
SP - 1603
EP - 1609
JO - Blood
JF - Blood
IS - 3
ER -