GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications

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 wit...

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Bibliographic Details
Published in:Iranian journal of immunology 2019-03, Vol.16 (2), p.127-141
Main Authors: Farahi, Lia, Ghaemimanesh, Fatemeh, Milani, Saeideh, Seyed Mohsen Razavi, Hadavi, Reza, Ali Ahmad Bayat, Salimi, Ali, Akhondi, Mohammad Mehdi, Rabbani, Hodjattallah
Format: Article
Language:English
Subjects:
Agent Orange
Annexin V
Apoptosis
Cell surface
Chronic lymphocytic leukemia
fibromodulin (fmod)
Flow cytometry
Glycosylphosphatidylinositol
Leukemia
Localization
Lymphatic leukemia
Lymphocytes B
Monoclonal antibodies
monoclonal antibody
Phosphatidylinositol
Phospholipase C
Propidium iodide
Therapeutic applications
Therapeutic targets
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Summary: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.
ISSN:1735-1383
1735-367X
DOI:10.22034/iji.2019.80256