BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner
BAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00594/full |
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| author | Eirini Sevdali Eleni Katsantoni Cristian R. Smulski Maria Moschovi Maria Palassopoulou Eleni-Nefeli Kolokotsa Nikoletta Argentou Nikolaos Giannakoulas Maria Adamaki Georgios Vassilopoulos Sophia Polychronopoulou Anastasios E. Germenis Hermann Eibel Matthaios Speletas |
| author_facet | Eirini Sevdali Eleni Katsantoni Cristian R. Smulski Maria Moschovi Maria Palassopoulou Eleni-Nefeli Kolokotsa Nikoletta Argentou Nikolaos Giannakoulas Maria Adamaki Georgios Vassilopoulos Sophia Polychronopoulou Anastasios E. Germenis Hermann Eibel Matthaios Speletas |
| author_sort | Eirini Sevdali |
| collection | DOAJ |
| description | BAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute lymphoblastic leukemia (B-ALL). Here, we evaluated the expression of this system in B-ALL and its involvement in spontaneous and drug-induced apoptosis of B-lymphoblasts, taking into consideration the distinct disease subtypes. We found that BAFFR is the most predominant aberrantly expressed receptor in B-ALL and that its expression, along with BCMA and APRIL, positively correlates with the maturation stage of B-lymphoblasts. Moreover, the binding of the E2A-PBX1 chimeric protein to the BAFFR promoter suggests that the transcriptional activator promotes the increase in BAFFR expression observed in about 50% of pre-B-ALL patients carrying the t(1, 19) translocation. BAFF binding to BAFFR led to the processing of NF-κB2 p100 in pre-B ALL cells suggesting that BAFFR can activate the NF-κB2 pathway in pre-B ALL cells. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL+ BAFFR+ pre-B-lymphoblasts in adult B-ALL. It also enhances glucocorticoid-induced apoptosis in the E2A-PBX1+ pre-B-ALL cell line 697. These data suggest that BAFF/BAFFR signaling in B-ALL cells differs from normal B cells and that it may affect the pathogenesis of the disease. |
| first_indexed | 2024-04-12T22:05:48Z |
| format | Article |
| id | doaj.art-e2086a125c6c4fdba9c4c6355537ebb0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T22:05:48Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e2086a125c6c4fdba9c4c6355537ebb02022-12-22T03:14:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-07-01910.3389/fonc.2019.00594439059BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype MannerEirini Sevdali0Eleni Katsantoni1Cristian R. Smulski2Maria Moschovi3Maria Palassopoulou4Eleni-Nefeli Kolokotsa5Nikoletta Argentou6Nikolaos Giannakoulas7Maria Adamaki8Georgios Vassilopoulos9Sophia Polychronopoulou10Anastasios E. Germenis11Hermann Eibel12Matthaios Speletas13Department of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceBasic Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceCenter for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg im Breisgau, GermanyHematology/Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, “Aghia Sophia” Children's Hospital, Athens, GreeceDepartment of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceHematology/Oncology Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, “Aghia Sophia” Children's Hospital, Athens, GreeceDepartment of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of Pediatric Hematology/Oncology, “Aghia Sophia” Children's Hospital, Athens, GreeceDepartment of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceCenter for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg im Breisgau, GermanyDepartment of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceBAFF, APRIL and their receptors regulate the survival, maturation and homeostasis of mature B-cells. Despite the lack of a functional role of BAFF/APRIL system during normal early B-cell development, previous studies indicated a contribution of these molecules in the pathogenesis of B-lineage acute lymphoblastic leukemia (B-ALL). Here, we evaluated the expression of this system in B-ALL and its involvement in spontaneous and drug-induced apoptosis of B-lymphoblasts, taking into consideration the distinct disease subtypes. We found that BAFFR is the most predominant aberrantly expressed receptor in B-ALL and that its expression, along with BCMA and APRIL, positively correlates with the maturation stage of B-lymphoblasts. Moreover, the binding of the E2A-PBX1 chimeric protein to the BAFFR promoter suggests that the transcriptional activator promotes the increase in BAFFR expression observed in about 50% of pre-B-ALL patients carrying the t(1, 19) translocation. BAFF binding to BAFFR led to the processing of NF-κB2 p100 in pre-B ALL cells suggesting that BAFFR can activate the NF-κB2 pathway in pre-B ALL cells. Surprisingly, we found that BAFF treatment promotes the cell death of primary BCR-ABL+ BAFFR+ pre-B-lymphoblasts in adult B-ALL. It also enhances glucocorticoid-induced apoptosis in the E2A-PBX1+ pre-B-ALL cell line 697. These data suggest that BAFF/BAFFR signaling in B-ALL cells differs from normal B cells and that it may affect the pathogenesis of the disease.https://www.frontiersin.org/article/10.3389/fonc.2019.00594/fullBAFFRB-ALLE2A-PBX1glucocorticoidsapoptosis |
| spellingShingle | Eirini Sevdali Eleni Katsantoni Cristian R. Smulski Maria Moschovi Maria Palassopoulou Eleni-Nefeli Kolokotsa Nikoletta Argentou Nikolaos Giannakoulas Maria Adamaki Georgios Vassilopoulos Sophia Polychronopoulou Anastasios E. Germenis Hermann Eibel Matthaios Speletas BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner Frontiers in Oncology BAFFR B-ALL E2A-PBX1 glucocorticoids apoptosis |
| title | BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner |
| title_full | BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner |
| title_fullStr | BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner |
| title_full_unstemmed | BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner |
| title_short | BAFF/APRIL System Is Functional in B-Cell Acute Lymphoblastic Leukemia in a Disease Subtype Manner |
| title_sort | baff april system is functional in b cell acute lymphoblastic leukemia in a disease subtype manner |
| topic | BAFFR B-ALL E2A-PBX1 glucocorticoids apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00594/full |
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