Correspondence
References Ansell, J., Hirsh, J., Hylek, E., Jacobson, A., Crowther, M. & Palareti, G. (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition). Chest, 133, 160S–198S. Cust odio das D^ ores, S.M., Booth, S.L., Martini, L.A., de Carvalho Gouv^ea, V.H., Padovani, C.R., de Abreu Maffei, F.H., Campana, A.O. & Rupp de Paiva, S.A. (2007) Relationship between diet and anticoagulant response to warfarin: a factor analysis. European Journal of Nutrition, 46, 147–154. Ferland, G., Sadowski, J.A. & O’Brien, M.E. (1993) Dietary induced subclinical vitamin K deficiency
in normal human subjects. The Journal of Clinical Investigation, 91, 1761–1768. Fujiwara, S. & Amisaki, T. (2011) Steric and allosteric effects of fatty acids on the binding of warfarin to human serum albumin revealed by molecular dynamics and free energy calculations. Chemical & Pharmaceutical Bulletin, 59, 860–867. Mehran, R., Rao, S.V., Bhatt, D.L., Gibson, C.M., Caixeta, A., Eikelboom, J., Kaul, S., Wiviott, S.D., Menon, V., Nikolsky, E., Serebruany, V., Valgimigli, M., Vranckx, P., Taggart, D., Sabik, J.F., Cutlip, D.E., Krucoff, M.W., Ohman, E.M., Steg, P.G. & White, H. (2011) Standardized bleeding definitions for cardiovascular clinical trials. Circulation, 123, 2736–2747.
Palareti, G. & Cosmi, B. (2009) Bleeding with anticoagulation therapy – Who is at risk, and how best to identify such patients. Thrombosis and Haemostasis, 102, 268–278. Schulman, S., Beyth, R.J., Kearon, C. & Levine, M.N., American College of Chest Physicians. (2008) Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 133 (6 Suppl), 257S–298S. Suttie, J.W., Mummah-Schendel, L.L., Shah, D.V., Lyle, B.J. & Greger, J.L. (1988) Vitamin K deficiency from dietary vitamin K restriction in humans. American Journal of Clinical Nutrition, 47, 475–480.
Gene expression profiles of central nervous system lymphoma predict poor survival in patients with diffuse large B-cell lymphoma
The overall prognosis of B-cell non-Hodgkin lymphoma has substantially improved since the introduction of rituximab. In the treatment of the patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy (R-CHOP) can achieve much better responses than CHOP alone (Coiffier et al, 2002; Pfreundschuh et al, 2006). In contrast with the effective treatment outcome of systemic lesions, central nervous system (CNS) involvement in DLBCL still poses an insufficient prognosis. One reason is that penetration of most of the chemotherapeutic agents, including rituximab, into CNS parenchyma is limited due to the blood-brain barrier. In addition to this problem of drug delivery, there is a possibility that lymphoma cells invading the CNS possess intrinsic resistance to chemotherapy. Recent studies have demonstrated that DLBCL can be divided into two major subgroups according to gene expression profile: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtype; the ABC group has a significantly poorer overall survival (OS) than the GCB group (Alizadeh et al, 2000). We hypothesized that primary CNS lymphoma (PCNSL) also has a characteristic gene expression profile, and investigated if the expression signature could predict prognosis in nodal DLBCL. To obtain a specific gene expression profile for PCNSL, we thoroughly investigated the genes whose expression levels are significantly increased or decreased in PCNSL compared with those in nodal lymphoma, extranodal lymphoma and normal lymph node using published microarray data deposited in GSE11392 and GSE25297 (Tun et al, 2008; Sung et al, 794
2011) of the Gene Expression Omnibus (GEO) database. A set of CEL files were downloaded from the GEO and normalized using the justRMA function from the Affy package of Bioconductor. The expression values of individual genes were compared between groups using RankProd analysis. Fifteen genes were selected as being significantly elevated or decreased in PCNSL compared with nodal lymphoma, extranodal lymphoma and normal lymph node, as determined by a false discovery rate
References Ansell, J., Hirsh, J., Hylek, E., Jacobson, A., Crowther, M. & Palareti, G. (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition). Chest, 133, 160S–198S. Cust odio das D^ ores, S.M., Booth, S.L., Martini, L.A., de Carvalho Gouv^ea, V.H., Padovani, C.R., de Abreu Maffei, F.H., Campana, A.O. & Rupp de Paiva, S.A. (2007) Relationship between diet and anticoagulant response to warfarin: a factor analysis. European Journal of Nutrition, 46, 147–154. Ferland, G., Sadowski, J.A. & O’Brien, M.E. (1993) Dietary induced subclinical vitamin K deficiency
in normal human subjects. The Journal of Clinical Investigation, 91, 1761–1768. Fujiwara, S. & Amisaki, T. (2011) Steric and allosteric effects of fatty acids on the binding of warfarin to human serum albumin revealed by molecular dynamics and free energy calculations. Chemical & Pharmaceutical Bulletin, 59, 860–867. Mehran, R., Rao, S.V., Bhatt, D.L., Gibson, C.M., Caixeta, A., Eikelboom, J., Kaul, S., Wiviott, S.D., Menon, V., Nikolsky, E., Serebruany, V., Valgimigli, M., Vranckx, P., Taggart, D., Sabik, J.F., Cutlip, D.E., Krucoff, M.W., Ohman, E.M., Steg, P.G. & White, H. (2011) Standardized bleeding definitions for cardiovascular clinical trials. Circulation, 123, 2736–2747.
Palareti, G. & Cosmi, B. (2009) Bleeding with anticoagulation therapy – Who is at risk, and how best to identify such patients. Thrombosis and Haemostasis, 102, 268–278. Schulman, S., Beyth, R.J., Kearon, C. & Levine, M.N., American College of Chest Physicians. (2008) Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 133 (6 Suppl), 257S–298S. Suttie, J.W., Mummah-Schendel, L.L., Shah, D.V., Lyle, B.J. & Greger, J.L. (1988) Vitamin K deficiency from dietary vitamin K restriction in humans. American Journal of Clinical Nutrition, 47, 475–480.
Gene expression profiles of central nervous system lymphoma predict poor survival in patients with diffuse large B-cell lymphoma
The overall prognosis of B-cell non-Hodgkin lymphoma has substantially improved since the introduction of rituximab. In the treatment of the patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy (R-CHOP) can achieve much better responses than CHOP alone (Coiffier et al, 2002; Pfreundschuh et al, 2006). In contrast with the effective treatment outcome of systemic lesions, central nervous system (CNS) involvement in DLBCL still poses an insufficient prognosis. One reason is that penetration of most of the chemotherapeutic agents, including rituximab, into CNS parenchyma is limited due to the blood-brain barrier. In addition to this problem of drug delivery, there is a possibility that lymphoma cells invading the CNS possess intrinsic resistance to chemotherapy. Recent studies have demonstrated that DLBCL can be divided into two major subgroups according to gene expression profile: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtype; the ABC group has a significantly poorer overall survival (OS) than the GCB group (Alizadeh et al, 2000). We hypothesized that primary CNS lymphoma (PCNSL) also has a characteristic gene expression profile, and investigated if the expression signature could predict prognosis in nodal DLBCL. To obtain a specific gene expression profile for PCNSL, we thoroughly investigated the genes whose expression levels are significantly increased or decreased in PCNSL compared with those in nodal lymphoma, extranodal lymphoma and normal lymph node using published microarray data deposited in GSE11392 and GSE25297 (Tun et al, 2008; Sung et al, 794
2011) of the Gene Expression Omnibus (GEO) database. A set of CEL files were downloaded from the GEO and normalized using the justRMA function from the Affy package of Bioconductor. The expression values of individual genes were compared between groups using RankProd analysis. Fifteen genes were selected as being significantly elevated or decreased in PCNSL compared with nodal lymphoma, extranodal lymphoma and normal lymph node, as determined by a false discovery rate
