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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. (1398). GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications. سامانه مدیریت نشریات علمی, 16(2), 127-141. doi: 10.22034/iji.2019.80256
Lia Farahi; Fatemeh Ghaemimanesh; Saeideh Milani; Seyed Mohsen Razavi; Reza Hadavi; Ali Ahmad Bayat; Ali Salimi; Mohammad Mehdi Akhondi; Hodjattallah Rabbani. "GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications". سامانه مدیریت نشریات علمی, 16, 2, 1398, 127-141. doi: 10.22034/iji.2019.80256
Farahi, Lia, Ghaemimanesh, Fatemeh, Milani, Saeideh, Razavi, Seyed Mohsen, Hadavi, Reza, Bayat, Ali Ahmad, Salimi, Ali, Akhondi, Mohammad Mehdi, Rabbani, Hodjattallah. (1398). 'GPI-Anchored Fibromodulin as a Novel Target in Chronic Lymphocytic Leukemia: Diagnostic and Therapeutic Implications', سامانه مدیریت نشریات علمی, 16(2), pp. 127-141. doi: 10.22034/iji.2019.80256
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. سامانه مدیریت نشریات علمی, 1398; 16(2): 127-141. doi: 10.22034/iji.2019.80256

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

Iranian Journal of Immunology
مقاله 4، دوره 16، شماره 2، شهریور 2019، صفحه 127-141    اصل مقاله (1.25 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22034/iji.2019.80256
نویسندگان
Lia Farahi1؛ Fatemeh Ghaemimanesh1؛ Saeideh Milani1؛ Seyed Mohsen Razavi2؛ Reza Hadavi1؛ Ali Ahmad Bayat1؛ Ali Salimi1؛ Mohammad Mehdi Akhondi1؛ Hodjattallah Rabbani* 1
1Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
2Clinic of Hematology and Oncology, Firoozgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
چکیده
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.
کلیدواژه‌ها
Apoptosis؛ Chronic Lymphocytic Leukemia؛ Fibromodulin (FMOD)؛ Glycosylphosphatidylinositol؛ Monoclonal Antibody
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