{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:10:44Z","timestamp":1793686244970,"version":"4.5.1"},"reference-count":29,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>GPR34 translocation and mutation are specifically associated with salivary gland MALT lymphoma (SG-MALT-lymphoma). The majority of GPR34 mutations are clustered in its C-terminus, resulting in truncated proteins lacking the phosphorylation motif important for receptor desensitization. It is unclear why GPR34 genetic changes associate with SG-MALT-lymphoma and how these mutations contribute to the development of lymphoma. We generated isogenic Flp-InTRex293 cell lines that stably expressed a single copy of GPR34 or its various mutants and performed a range of in vitro assays. We found that the GPR34 Q340X truncation, but not the R84H and D151A mutants, conferred a significantly increased resistance to apoptosis and greater transforming potential than the GPR34 wild type. The GPR34 truncation mutant had a significantly delayed internalization compared with the wild type after ligand (lysophosphatidylserine) stimulation. Among the 9 signaling pathways examined, the GPR34 Q340X truncation, and to a lesser extent the D151A mutant, significantly activated CRE, NF-\u03baB, and AP1 reporter activities, particularly in the presence of ligand stimulation. We further described the enhanced activities of phospholipase-A1\/2 in the culture supernatant of Flp-InTRex293 cells that expressed the GPR34 Q340X mutant, as well as their potential to catalyze the synthesis of lysophosphatidylserine from phosphatidylserine. Importantly, phospholipase-A1 was abundantly expressed in the duct epithelium of salivary glands and those involved in lymphoepithelial lesions (LELs). Our findings advocate a model of paracrine stimulation of malignant B cells via GPR34, in which phospholipase A is released by LELs and hydrolyzes the phosphatidylserine exposed on apoptotic cells, generating lysophosphatidylserine, the ligand for GPR34. Thus, GPR34 activation potentially bridges LELs to genesis of SG-MALT-lymphoma.<\/jats:p>","DOI":"10.1182\/blood.2020010495","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T20:12:53Z","timestamp":1622837573000},"page":"2186-2197","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":24,"title":["GPR34 activation potentially bridges lymphoepithelial lesions to genesis of salivary gland MALT lymphoma"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5429-4882","authenticated-orcid":false,"given":"Boguslawa","family":"Korona","sequence":"first","affiliation":[{"name":"Division of Cellular and Molecular Pathology, Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmara","family":"Korona","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge, Cambridge, United 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