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Journal of Neuro-Oncology

, Volume 121, Issue 2, pp 289–296 | Cite as

Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system

  • Ariz Akhter
  • Noraidah Masir
  • Ghaleb Elyamany
  • Kean-Chang Phang
  • Etienne Mahe
  • Ali Matar Al-Zahrani
  • Meer-Taher Shabani-Rad
  • Douglas Allan Stewart
  • Adnan MansoorEmail author
Laboratory Investigation

Abstract

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P < 0.0001). When compared with systemic DLBCL samples, higher expression of TLR9, CD79B, CARD11, LYN and BLNK was noted in CNS DLBCL (>1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL.

Keywords

Primary central nervous system lymphoma Toll-like receptor B-cell receptor MYD88 mutations nCounter analysis 

Notes

Acknowledgments

This study was funded through Alberta Cancer Foundation Grant ##25999. Dana Impak Perdana DIP2012-10/3, University Kebangsaan Malaysia, supported N. Masir and K.C. Phang. Authors would like to acknowledge Calgary Laboratory Services (CLS) for technical support and Mr. Thomas Kryton of University of Calgary, for providing assistance with the artwork.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ariz Akhter
    • 1
  • Noraidah Masir
    • 2
  • Ghaleb Elyamany
    • 3
  • Kean-Chang Phang
    • 2
  • Etienne Mahe
    • 1
  • Ali Matar Al-Zahrani
    • 3
  • Meer-Taher Shabani-Rad
    • 1
  • Douglas Allan Stewart
    • 4
  • Adnan Mansoor
    • 1
    • 5
    Email author
  1. 1.Division of Hematology and Transfusion Medicine, Department of Pathology and Laboratory MedicineUniversity of Calgary/Calgary Laboratory Services (CLS)CalgaryCanada
  2. 2.Department of Pathology, Faculty of MedicineUniversity Kebangsaan MalaysiaKuala LumpurMalaysia
  3. 3.Department of Pathology and Laboratory Medicine (GE) and Oncology (AZ)Prince Sultan Military Medical CityRiyadhSaudi Arabia
  4. 4.Division of Hematology, Department of MedicineUniversity of Calgary/Tom Baker Cancer CenterCalgaryCanada
  5. 5.Rm C614, Foothills Medical CentreCalgaryCanada

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