Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma
- 30 September 2010
- journal article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 96 (1), 87-95
- https://doi.org/10.3324/haematol.2010.030296
Abstract
Background Proliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds. Design and Methods We assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores. Results In the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progression-associated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P2-microglobulin, International Staging System stage, associated high-risk chromosomal aberrations, e.g. translocation t(4;14), and gene expression-based high-risk scores. Conclusions Proliferation assessed by gene expression profiling, being independent of serum-β2-microglobulin, International Staging System stage, t(4;14), and gene expression-based risk scores, is a central prognostic factor in multiple myeloma. Surrogating a biological targetable variable, gene expression-based assessment of proliferation allows selection of patients for risk-adapted anti-proliferative treatment on the background of conventional and gene expression-based risk factors.Keywords
This publication has 42 references indexed in Scilit:
- Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesisOncogene, 2009
- Induction of angiogenesis by normal and malignant plasma cellsBlood, 2009
- Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myelomaBlood, 2009
- Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du MyélomeBlood, 2007
- The molecular classification of multiple myelomaBlood, 2006
- Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantationBlood, 2006
- Cyclin D dysregulation: an early and unifying pathogenic event in multiple myelomaBlood, 2005
- Recycling the Cell CycleCell, 2004
- Measurement of apoptosis and proliferation of bone marrow plasma cells in patients with plasma cell proliferative disordersBritish Journal of Haematology, 1999
- CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATIONBritish Journal of Haematology, 1998