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Disease stage‐specific G protein‐coupled receptor expression in clinical disorders: Chronic lymphocytic leukemia as a model
Author(s) -
Katakia Trishna,
Murray Fiona,
Zhang Lingzhi,
Gray Charles,
Insel Paul
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1038.5
Subject(s) - g protein coupled receptor , chronic lymphocytic leukemia , receptor , biology , disease , ighv@ , cancer research , leukemia , immunology , bioinformatics , medicine , genetics
G protein‐coupled receptors (GPCRs) are attractive targets in disease since they are expressed on the plasma membrane and show tissue‐specific expression. A clinical problem for many heterogeneous diseases, such as Chronic lymphocytic leukemia (CLL), is the lack of markers that can predict prognosis. CLL, which is characterized by the accumulation of B‐cells, is classified as aggressive, which requires immediate treatment, or indolent, which does not require treatment. We hypothesized that patterns of GPCR expression are disease stage‐specific and used CLL as a model to test if such patterns can identify biomarkers and therapeutic targets. Using a TaqMan® GPCR array we found that normal B‐cells (n=10) express greater than 200 GPCRs (74 orphan receptors), indolent CLL cells (n=10) express greater than 170 GPCRs (74 orphan GPCRs) and aggressive CLL cells (n=10) express greater than 117 GPCRs (51 orphan GPCRs). Numerous GPCRs were uniquely expressed or altered in CLL and expression differed in the 2 stages of CLL. Expression of vasoactive intestinal polypeptide receptor 1 (VIPR1), a Gs‐coupled GPCR, increased >700‐fold in aggressive CLL compared to indolent, and VIP (1 μM, 48h) induced apoptosis of CLL cells (P<0.05, n=3). Thus, expression of particular GPCRs can provide stage‐specific markers and identify novel targets for the treatment of CLL or other heterogeneous diseases. Funded by NIH.