Iranian Journal of Immunology

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

Document Type : Original Article

Authors

Lia Farahi 1
Fatemeh Ghaemimanesh 1
Saeideh Milani 1
Seyed Mohsen Razavi 2
Reza Hadavi 1
Ali Ahmad Bayat 1
Ali Salimi 1
Mohammad Mehdi Akhondi 1
Hodjattallah Rabbani 1

1 Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

2 Clinic of Hematology and Oncology, Firoozgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

https://doi.org/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
Iranian Journal of Immunology
Volume 16, Issue 2
Spring 2019
Pages 127-141

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