Blood Journal
Leading the way in experimental and clinical research in hematology

t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

  1. Stephen M. Ansell1,*,
  2. Takashi Akasaka2,
  3. Ellen McPhail3,
  4. Michelle Manske1,
  5. Esteban Braggio5,
  6. Tammy Price-Troska1,
  7. Steven Ziesmer1,
  8. Frank Secreto1,
  9. Rafael Fonseca5,
  10. Mamta Gupta1,
  11. Mark Law3,
  12. Thomas E. Witzig1,
  13. Martin J. S. Dyer2,
  14. Ahmet Dogan4,
  15. James R. Cerhan6, and
  16. Anne J. Novak1,*
  1. 1Division of Hematology, Mayo Clinic, Rochester, MN;
  2. 2MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom;
  3. Divisions of 3Hematopathology, and
  4. 4Anatomic Pathology, Mayo Clinic, Rochester, MN;
  5. 5Division of Hematology, Mayo Clinic, Scottsdale, AZ; and
  6. 6Division of Epidemiology, Mayo Clinic, Rochester, MN


Genetic aberrations, including trisomies 3 and 18, and well-defined IGH translocations, have been described in marginal zone lymphomas (MZLs); however, these known genetic events are present in only a subset of cases. Here, we report the cloning of an IGH translocation partner on chromosome X, t(X;14)(p11.4;q32) that deregulates expression of an poorly characterized orphan G-protein–coupled receptor, GPR34. Elevated GPR34 gene expression was detected independent of the translocation in multiple subtypes of non-Hodgkin lymphoma and distinguished a unique molecular subtype of MZL. Increased expression of GPR34 was also detected in tissue from brain tumors and surface expression of GPR34 was detected on human MZL tumor cells and normal immune cells. Overexpression of GPR34 in lymphoma and HeLa cells resulted in phosphorylation of ERK, PKC, and CREB; induced CRE, AP1, and NF-κB–mediated gene transcription; and increased cell proliferation. In summary, these results are the first to identify a role for a GPR34 in lymphoma cell growth, provide insight into GPR34-mediated signaling, identify a genetically unique subset of MZLs that express high levels of GPR34, and suggest that MEK inhibitors may be useful for treatment of GPR34-expressing tumors.

  • Submitted November 7, 2011.
  • Accepted August 27, 2012.
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