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

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Farahi Lia; GHAEMIMANESH FATEMEH; MILANI SAEIDEH; RAZAVI SEYED MOHSEN; HADAVI REZA; BAYAT ALI AHMAD; SALIMI ALI; AKHONDI MOHAMMAD MEHDI; RABBANI HODJATTALLAH

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Journal: Iranian Journal of Immunology Year:2019 | Volume:16 | Issue:2 Page(s): 127-141

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Title

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

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Keywords

Apoptosis

Chronic Lymphocytic Leukemia

Fibromodulin (FMOD)

Glycosylphosphatidylinositol

Monoclonal Antibody

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.

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APA: Copy

Farahi, Lia, GHAEMIMANESH, FATEMEH, MILANI, SAEIDEH, RAZAVI, SEYED MOHSEN, HADAVI, REZA, BAYAT, ALI AHMAD, SALIMI, ALI, AKHONDI, MOHAMMAD MEHDI, & RABBANI, HODJATTALLAH. (2019). GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications. IRANIAN JOURNAL OF IMMUNOLOGY (IJI), 16(2), 127-141. SID. https://sid.ir/paper/296917/en

Vancouver: Copy

Farahi Lia, GHAEMIMANESH FATEMEH, MILANI SAEIDEH, RAZAVI SEYED MOHSEN, HADAVI REZA, BAYAT ALI AHMAD, SALIMI ALI, AKHONDI MOHAMMAD MEHDI, RABBANI HODJATTALLAH. GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications. IRANIAN JOURNAL OF IMMUNOLOGY (IJI)[Internet]. 2019;16(2):127-141. Available from: https://sid.ir/paper/296917/en

IEEE: Copy

Lia Farahi, FATEMEH GHAEMIMANESH, SAEIDEH MILANI, SEYED MOHSEN RAZAVI, REZA HADAVI, ALI AHMAD BAYAT, ALI SALIMI, MOHAMMAD MEHDI AKHONDI, and HODJATTALLAH RABBANI, “GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications,” IRANIAN JOURNAL OF IMMUNOLOGY (IJI), vol. 16, no. 2, pp. 127–141, 2019, [Online]. Available: https://sid.ir/paper/296917/en

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