ABERRANT BAFF-R EXPRESSION AFFECTS APOPTOSIS RATE OF B LYMPHOBLASTS AFTER CORTICOSTEROID TREATMENT
(Abstract release date: 05/21/15)
EHA Library. Speletas M. 06/12/15; 103023; PB1595
Disclosure(s): University of Thessaly, School of Health Sciences, Faculty of Medicine
Matthaios Speletas
Contributions
Contributions
Abstract
Abstract: PB1595
Type: Publication Only
Background
BAFF and APRIL play crucial role in the survival, maturation and homeostasis of peripheral B-cells through their interactions with BAFF-R, TACI and BCMA receptors. While the BAFF/APRIL cytokine axis lacks functional roles in early stages of normal B cell development, recent evidence indicates that malignant lymphoblasts aberrantly express receptors of the BAFF-system (predominantly BAFF-R), suggesting a new role for these molecules in acute lymphoblastic leukemia (ALL) biology.
Aims
The aim of this study was to uncover any possible effect of BAFFR aberrant expression on the in vitro survival capacity of malignant lymphoblasts after treatment with conventional chemotherapeutic drugs.
Methods
Two ALL cell lines were included in the study?: the pre-B-ALL cell line 697, expressing BAFF-R and carrying the E2A-PBX1 chromosomal translocation and the T- ALL Jurkat cell line, characterized by the absence of expression of any BAFF/APRIL receptor (served also as a negative control). Cells have been treated in the presence of chemotherapeutic agents that are currently being used in ALL therapeutic protocols (aracytine and dexamethasone). The hypotoxic dose of these drugs (aracytine: 0.08-40.0 μg/ml, dexamethasone: 0.01-200.0 μg/ml) was determined by evaluating the apoptosis rate of cells with flow cytometry, using an Annexin V-FITC/7-AAD kit (Beckman-Coulter), according to the manusfacturer's instructions. In order to determine if the presence of BAFF could affect the survival of ALL cell lines, cells have been treated with exogenous BAFF (5 ng/ml - 800 ng/ml), in combination or not with one of the above agents.
Results
Dexamethazone induced apoptosis of both cell lines in a dose-dependent manner. Interestingly enough, exogenous BAFF significantly increased the dexamethasone-induced apoptosis of 697 cells; this effect was also obvious in the lowest dose of BAFF (5ng/mL). As expected, exogenous BAFF did not affect the rate of dexamethasone-induced apoptosis in Jurkat cells, which did not express BAFF-R. Concerning aracytine, treatment of both cell lines with BAFF did not alter the apoptosis rate caused by the drug itself.
Summary
The aberrant expression of BAFFR might play a crucial role in ALL biology and treatment.
Keyword(s): Acute lymphoblastic leukemia, BAFF, Corticosteroids
Session topic: Publication Only
Type: Publication Only
Background
BAFF and APRIL play crucial role in the survival, maturation and homeostasis of peripheral B-cells through their interactions with BAFF-R, TACI and BCMA receptors. While the BAFF/APRIL cytokine axis lacks functional roles in early stages of normal B cell development, recent evidence indicates that malignant lymphoblasts aberrantly express receptors of the BAFF-system (predominantly BAFF-R), suggesting a new role for these molecules in acute lymphoblastic leukemia (ALL) biology.
Aims
The aim of this study was to uncover any possible effect of BAFFR aberrant expression on the in vitro survival capacity of malignant lymphoblasts after treatment with conventional chemotherapeutic drugs.
Methods
Two ALL cell lines were included in the study?: the pre-B-ALL cell line 697, expressing BAFF-R and carrying the E2A-PBX1 chromosomal translocation and the T- ALL Jurkat cell line, characterized by the absence of expression of any BAFF/APRIL receptor (served also as a negative control). Cells have been treated in the presence of chemotherapeutic agents that are currently being used in ALL therapeutic protocols (aracytine and dexamethasone). The hypotoxic dose of these drugs (aracytine: 0.08-40.0 μg/ml, dexamethasone: 0.01-200.0 μg/ml) was determined by evaluating the apoptosis rate of cells with flow cytometry, using an Annexin V-FITC/7-AAD kit (Beckman-Coulter), according to the manusfacturer's instructions. In order to determine if the presence of BAFF could affect the survival of ALL cell lines, cells have been treated with exogenous BAFF (5 ng/ml - 800 ng/ml), in combination or not with one of the above agents.
Results
Dexamethazone induced apoptosis of both cell lines in a dose-dependent manner. Interestingly enough, exogenous BAFF significantly increased the dexamethasone-induced apoptosis of 697 cells; this effect was also obvious in the lowest dose of BAFF (5ng/mL). As expected, exogenous BAFF did not affect the rate of dexamethasone-induced apoptosis in Jurkat cells, which did not express BAFF-R. Concerning aracytine, treatment of both cell lines with BAFF did not alter the apoptosis rate caused by the drug itself.
Summary
The aberrant expression of BAFFR might play a crucial role in ALL biology and treatment.
Keyword(s): Acute lymphoblastic leukemia, BAFF, Corticosteroids
Session topic: Publication Only
Abstract: PB1595
Type: Publication Only
Background
BAFF and APRIL play crucial role in the survival, maturation and homeostasis of peripheral B-cells through their interactions with BAFF-R, TACI and BCMA receptors. While the BAFF/APRIL cytokine axis lacks functional roles in early stages of normal B cell development, recent evidence indicates that malignant lymphoblasts aberrantly express receptors of the BAFF-system (predominantly BAFF-R), suggesting a new role for these molecules in acute lymphoblastic leukemia (ALL) biology.
Aims
The aim of this study was to uncover any possible effect of BAFFR aberrant expression on the in vitro survival capacity of malignant lymphoblasts after treatment with conventional chemotherapeutic drugs.
Methods
Two ALL cell lines were included in the study?: the pre-B-ALL cell line 697, expressing BAFF-R and carrying the E2A-PBX1 chromosomal translocation and the T- ALL Jurkat cell line, characterized by the absence of expression of any BAFF/APRIL receptor (served also as a negative control). Cells have been treated in the presence of chemotherapeutic agents that are currently being used in ALL therapeutic protocols (aracytine and dexamethasone). The hypotoxic dose of these drugs (aracytine: 0.08-40.0 μg/ml, dexamethasone: 0.01-200.0 μg/ml) was determined by evaluating the apoptosis rate of cells with flow cytometry, using an Annexin V-FITC/7-AAD kit (Beckman-Coulter), according to the manusfacturer's instructions. In order to determine if the presence of BAFF could affect the survival of ALL cell lines, cells have been treated with exogenous BAFF (5 ng/ml - 800 ng/ml), in combination or not with one of the above agents.
Results
Dexamethazone induced apoptosis of both cell lines in a dose-dependent manner. Interestingly enough, exogenous BAFF significantly increased the dexamethasone-induced apoptosis of 697 cells; this effect was also obvious in the lowest dose of BAFF (5ng/mL). As expected, exogenous BAFF did not affect the rate of dexamethasone-induced apoptosis in Jurkat cells, which did not express BAFF-R. Concerning aracytine, treatment of both cell lines with BAFF did not alter the apoptosis rate caused by the drug itself.
Summary
The aberrant expression of BAFFR might play a crucial role in ALL biology and treatment.
Keyword(s): Acute lymphoblastic leukemia, BAFF, Corticosteroids
Session topic: Publication Only
Type: Publication Only
Background
BAFF and APRIL play crucial role in the survival, maturation and homeostasis of peripheral B-cells through their interactions with BAFF-R, TACI and BCMA receptors. While the BAFF/APRIL cytokine axis lacks functional roles in early stages of normal B cell development, recent evidence indicates that malignant lymphoblasts aberrantly express receptors of the BAFF-system (predominantly BAFF-R), suggesting a new role for these molecules in acute lymphoblastic leukemia (ALL) biology.
Aims
The aim of this study was to uncover any possible effect of BAFFR aberrant expression on the in vitro survival capacity of malignant lymphoblasts after treatment with conventional chemotherapeutic drugs.
Methods
Two ALL cell lines were included in the study?: the pre-B-ALL cell line 697, expressing BAFF-R and carrying the E2A-PBX1 chromosomal translocation and the T- ALL Jurkat cell line, characterized by the absence of expression of any BAFF/APRIL receptor (served also as a negative control). Cells have been treated in the presence of chemotherapeutic agents that are currently being used in ALL therapeutic protocols (aracytine and dexamethasone). The hypotoxic dose of these drugs (aracytine: 0.08-40.0 μg/ml, dexamethasone: 0.01-200.0 μg/ml) was determined by evaluating the apoptosis rate of cells with flow cytometry, using an Annexin V-FITC/7-AAD kit (Beckman-Coulter), according to the manusfacturer's instructions. In order to determine if the presence of BAFF could affect the survival of ALL cell lines, cells have been treated with exogenous BAFF (5 ng/ml - 800 ng/ml), in combination or not with one of the above agents.
Results
Dexamethazone induced apoptosis of both cell lines in a dose-dependent manner. Interestingly enough, exogenous BAFF significantly increased the dexamethasone-induced apoptosis of 697 cells; this effect was also obvious in the lowest dose of BAFF (5ng/mL). As expected, exogenous BAFF did not affect the rate of dexamethasone-induced apoptosis in Jurkat cells, which did not express BAFF-R. Concerning aracytine, treatment of both cell lines with BAFF did not alter the apoptosis rate caused by the drug itself.
Summary
The aberrant expression of BAFFR might play a crucial role in ALL biology and treatment.
Keyword(s): Acute lymphoblastic leukemia, BAFF, Corticosteroids
Session topic: Publication Only
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