ArticlePloS one2013
Proof of the concept to use a malignant B cell line drug screen strategy for identification and weight of melphalan resistance genes in multiple myeloma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- A bendamustine resistance gene signature in diffuse large B-cell lymphoma and multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Development of a Precision Medicine Workflow in Hematological Cancers, Aalborg University Hospital, Denmark.Cancers · 2020Article
- A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.Blood advances · 2018Article
- Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission.Experimental hematology & oncology · 2017Article
- The myeloma stem cell concept, revisited: from phenomenology to operational terms.Haematologica · 2016Review
- Gene Expression Profiles in Myeloma: Ready for the Real World?Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- Evaluation of in vitro effects of various targeted drugs on plasma cells and putative neoplastic stem cells in patients with multiple myeloma.Oncotarget · 2016Article
- hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine.PloS one · 2016Article
- Diffuse large B-cell lymphoma classification system that associates normal B-cell subset phenotypes with prognosis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
In a conceptual study of drug resistance we have used a preclinical model of malignant B-cell lines by combining drug induced growth inhibition and gene expression profiling. In the current report a melphalan resistance profile of 19 genes were weighted by microarray data from the MRC Myeloma IX trial and time to progression following high dose melphalan, to generate an individual melphalan resistance index. The resistance index was subsequently validated in the HOVON65/GMMG-HD4 trial data set to prove the concept. Biologically, the assigned resistance indices were differentially distributed among translocations and cyclin D expression classes. Clinically, the 25% most melphalan resistant, the intermediate 50% and the 25% most sensitive patients had a median progression free survival of 18, 32 and 28 months, respectively (log-rank P-value = 0.05). Furthermore, the median overall survival was 45 months for the resistant group and not reached for the intermediate and sensitive groups (log-rank P-value = 0.003) following 38 months median observation. In a multivariate analysis, correcting for age, sex and ISS-staging, we found a high resistance index to be an independent variable associated with inferior progression free survival and overall survival. This study provides clinical proof of concept to use in vitro drug screen for identification of melphalan resistance gene signatures for future functional analysis.
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