Blood · 2005
Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome.
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Ladetto Marco, Vallet Sonia, Trojan Andreas, Dell'Aquila Maria, Monitillo Luigia, Rosato Rosalba, Santo Loredana, Drandi Daniela, Bertola Alessandra, Falco Patrizia, Cavallo Federica, Ricca Irene, De Marco Federica, Mantoan Barbara, Bode-Lesniewska Beata, Pagliano Gloria, Francese Roberto, Rocci Alberto, Astolfi Monica, Compagno Mara, Mariani Sara, Godio Laura, Marino Lydia, Ruggeri Marina, Omedè Paola, Palumbo Antonio, Boccadoro Mario
Аннотация
Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators. We thus decided to investigate the involvement of COX-2 in this neoplasm. Western blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM and monoclonal gammopathy of undetermined significance (MGUS). Selected cases under-went further evaluation by WB on purified CD138(+) cells, immunohistochemistry (IC), and real-time polymerase chain reaction (PCR) for mRNA expression. COX-2 was expressed in 11% (2 of 18) of MGUS specimens, 31% (29 of 94) of MM at diagnosis, and 47% (14 of 30) of MM with relapsed/refractory disease. COX-2 positivity was associated with a poor outcome in terms of progression-free (18 vs 36 months; P < .001) and overall survival (28 vs 52 months; P < .05). Real-time PCR showed COX-2 mRNA overexpression. IC and cell separation studies demonstrated COX-2 expression to be restricted to malignant plasma cells. This is the first report of the presence and prognostic role of COX-2 expression in MM. Future studies will assess COX-2 involvement in other hematologic tumors and its potential use as a therapeutic or chemo-preventive target in onco-hematology.
Предметные рубрики MeSH
AdultAgedBlotting, WesternBone Marrow CellsCell Line, TumorCyclooxygenase 2DNA, ComplementaryDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansImmunohistochemistryInflammationMaleMembrane GlycoproteinsMembrane ProteinsMiddle AgedMultiple MyelomaPrognosisProstaglandin-Endoperoxide SynthasesProteoglycansRNA, MessengerRecurrenceReverse Transcriptase Polymerase Chain ReactionSyndecan-1SyndecansTime FactorsTreatment Outcome