@article { author = {Farahi, Lia and Ghaemimanesh, Fatemeh and Milani, Saeideh and Razavi, Seyed Mohsen and Hadavi, Reza and Bayat, Ali Ahmad and Salimi, Ali and Akhondi, Mohammad Mehdi and Rabbani, Hodjattallah}, title = {GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications}, journal = {Iranian Journal of Immunology}, volume = {16}, number = {2}, pages = {127-141}, year = {2019}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {10.22034/iji.2019.80256}, abstract = {Background: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with glycosylphosphatidylinositol (GPI). Objective: To evaluate FMOD as a new biomarker in CLL patients in comparison with healthy individuals. Methods: A monoclonal antibody was generated against human FMOD. The cell surface expression of FMOD in 52 CLL patients and 45 healthy individuals were compared by flow cytometry. A bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) was used to determine the cell surface localization of FMOD using ELISA and flow cytometry techniques. Annexin V-FITC and propidium iodide (PI) was used to detect apoptosis induction in CLL PBMCs following in vitro incubation with anti-FMOD mAb. Results: The results demonstrated the widespread cell surface expression of GPI-anchored FMOD in CLL patients (median: 79.9 %), although healthy individuals had low FMOD expression (median: 6.2 %) (p≤0.0001). The cut-off value of FMOD expression was estimated with high sensitivity and specificity at 17.9%. Furthermore, in vitro apoptosis induction of leukemic cells following incubation with anti-FMOD mAb showed a direct apoptosis of CLL cells (27.9%) with very low effect on healthy PBMCs (6%). Conclusion: The membrane-anchoring of FMOD by means of a GPI moiety in leukemic cells supports FMOD as a highly potential diagnostic and therapeutic target in CLL patients.}, keywords = {apoptosis,Chronic lymphocytic leukemia,Fibromodulin (FMOD),Glycosylphosphatidylinositol,Monoclonal antibody}, url = {https://iji.sums.ac.ir/article_44938.html}, eprint = {https://iji.sums.ac.ir/article_44938_825b6bb75b89764912d0dbc21960c748.pdf} }