Abstract
Thrombosis portends a poor prognosis in individuals with solid tumors. Constitutive expression of tissue factor (TF) by cancer cells is a key in triggering activation of coagulation and promoting aggressive tumor behavior. Though multiple myeloma (MM) is associated with a high frequency of thrombosis in the context of thalidomide and lenalidomide therapy, prognosis is not affected by its occurrence. We sought to determine the expression of TF in MM. F3 (TF gene) expression profiling was analyzed in 55 human MM cell lines (HMCL) and in 223 solid tumor cell lines obtained from GlaxoSmithKline (GSK) Cancer Cell Line Genomic Profiling Dataset. TF was not expressed in any of the 55 HMCLs studied, in sharp contrast to solid tumors, 90% of which showed TF expression. F3 expression was also absent in tumor samples from 239 MM patients. Immunohistochemistry for TF was negative, with either no or focal (1+) staining in 70/73 MM patients. Only three marrow biopsies were moderately (2+) positive either focally or diffusely, suggesting that in rare cases bone marrow microenvironment may support TF expression. General lack of TF expression by neoplastic plasma cells may explain why thrombosis is not predictive of poor outcome, and why aspirin prophylaxis is often effective in MM.
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Acknowledgements
We would like to acknowledge GSK for making publicly available the Cancer Cell Line Genomic Profiling Data used in this study.
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GCM designed and analyzed research and wrote paper, EB designed and analyzed research and wrote paper, HM designed and analyzed research and RF designed and analyzed research and wrote paper.
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RF is a consultant for Genzyme, Medtronic, BMS, Amgen, Otsuka, Celgene, Intellikine and Lilly (all <$10 000). RF receives research support from Cylene, Onyx and Celgene. The remaining authors declare no conflict of interest.
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Cesarman-Maus, G., Braggio, E., Maldonado, H. et al. Absence of tissue factor expression by neoplastic plasma cells in multiple myeloma. Leukemia 26, 1671–1674 (2012). https://doi.org/10.1038/leu.2012.43
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DOI: https://doi.org/10.1038/leu.2012.43