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Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma.

Linderoth, Johan LU ; Edén, Patrik LU ; Ehinger, Mats LU ; Valcich, Jeanette LU ; Jerkeman, Mats LU ; Bendahl, Pär-Ola LU ; Berglund, Mattias; Enblad, Gunilla; Erlanson, Martin and Roos, Göran, et al. (2008) In British Journal of Haematology 141(4). p.423-432
Abstract
In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and... (More)
In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL. (Less)
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publication status
published
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in
British Journal of Haematology
volume
141
issue
4
pages
423 - 432
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000255059700002
  • pmid:18419622
  • scopus:42249094550
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2008.07037.x
language
English
LU publication?
yes
id
8ffb521b-7857-4d2a-8758-87e3c905d6c0 (old id 1147276)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18419622?dopt=Abstract
date added to LUP
2008-05-06 14:05:43
date last changed
2017-11-19 04:17:23
@article{8ffb521b-7857-4d2a-8758-87e3c905d6c0,
  abstract     = {In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.},
  author       = {Linderoth, Johan and Edén, Patrik and Ehinger, Mats and Valcich, Jeanette and Jerkeman, Mats and Bendahl, Pär-Ola and Berglund, Mattias and Enblad, Gunilla and Erlanson, Martin and Roos, Göran and Cavallin-Ståhl, Eva},
  issn         = {0007-1048},
  language     = {eng},
  number       = {4},
  pages        = {423--432},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma.},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2008.07037.x},
  volume       = {141},
  year         = {2008},
}