MULTIPLE NF-KB INDUCERS PROMOTE C-MYC-DEPENDENT B-CELL LYMPHOMAGENESIS.
(Abstract release date: 05/19/16)
EHA Library. Arnaud N. 06/09/16; 132931; E1382
Mr. Nicolas Arnaud
Contributions
Contributions
Abstract
Abstract: E1382
Type: Eposter Presentation
Background
Not only Burkitt lymphoma (BL) with the translocation of MYC, but also diffuse large B-cell lymphoma (DLBCL) by other mechanisms (mutation, amplification, promoter dysregulation…) are associated with dysregulation of c-Myc, the master transcription factor for proliferation. DLBCL’s are classified in two subgroups: “Germinal center B-cell” (GCB) without and “activated B-cell” (ABC) with constitutive NF-kappa B activation. This constitutive activation of NF-kappa B can be the result of genetic alterations (MYD88, A20, TRAF2, and TRAF5) or the activation of B-cell receptor or CD40. These features raise the question of the synergy between NF-kappa B and c-Myc in ABC DLBCL. By inducing c-Myc and NF-kappa B, via in particular, the viral oncogene LMP1 (Latent Membrane Protein 1), Epstein-Barr virus (EBV) immortalized B cells are another example of the coexistence of these two transcription factors in continuous proliferating B-cells. Although BL are described without NF-kappa B activation, frequent association with EBV raises the question of the role of NF-kappa B activation during the early phase of the oncogenic process.
Aims
To study the synergy between NF-kappa B and c-Myc using the effect of several NF-kappa B drivers in the context of a continuous activation of c-Myc.
Methods
In vitro, study of an EBV and c-Myc double inducible human B-cell model and Burkitt lymphoma cell lines. Ex vivo and in vivo, study of TLR9 activation of B cells from the λ-c-Myc transgenic mouse model. In vivo, study of double transgenic mouse model with constitutive activation of CD40 and c-Myc (mouse CD40 / Myc). Techniques used are those for studying functional proliferation, apoptosis, B-cel-differentiation, expression of protein and regulation of genes.
Results
Our results show that induction of NF-kappa B in the context of overexpression of c-Myc, i) by EBV latency III program, provides a selective advantage to those cells (gene expression in favor of a high metabolism, intense proliferation and protection against apoptosis), ii) by TLR9 (in vivo and in vitro model) increases the survival and proliferation of B lymphocytes of λ-c-Myc mice (increase of activated B cells, splenomegaly, increased B cells proliferation), and iii) by CD40 in the double transgenic CD40/Myc mice have a very aggressive B lymphomagenesis with in vivo increased proliferation and tumorigenesis.
Conclusion
We concluded that, whatever the tested model, NF-kappa B and c-Myc are functionally synergistic for transformation B cells.
Session topic: E-poster
Keyword(s): Lymphoma, Lymphomagenesis, MYC, NF- B
Type: Eposter Presentation
Background
Not only Burkitt lymphoma (BL) with the translocation of MYC, but also diffuse large B-cell lymphoma (DLBCL) by other mechanisms (mutation, amplification, promoter dysregulation…) are associated with dysregulation of c-Myc, the master transcription factor for proliferation. DLBCL’s are classified in two subgroups: “Germinal center B-cell” (GCB) without and “activated B-cell” (ABC) with constitutive NF-kappa B activation. This constitutive activation of NF-kappa B can be the result of genetic alterations (MYD88, A20, TRAF2, and TRAF5) or the activation of B-cell receptor or CD40. These features raise the question of the synergy between NF-kappa B and c-Myc in ABC DLBCL. By inducing c-Myc and NF-kappa B, via in particular, the viral oncogene LMP1 (Latent Membrane Protein 1), Epstein-Barr virus (EBV) immortalized B cells are another example of the coexistence of these two transcription factors in continuous proliferating B-cells. Although BL are described without NF-kappa B activation, frequent association with EBV raises the question of the role of NF-kappa B activation during the early phase of the oncogenic process.
Aims
To study the synergy between NF-kappa B and c-Myc using the effect of several NF-kappa B drivers in the context of a continuous activation of c-Myc.
Methods
In vitro, study of an EBV and c-Myc double inducible human B-cell model and Burkitt lymphoma cell lines. Ex vivo and in vivo, study of TLR9 activation of B cells from the λ-c-Myc transgenic mouse model. In vivo, study of double transgenic mouse model with constitutive activation of CD40 and c-Myc (mouse CD40 / Myc). Techniques used are those for studying functional proliferation, apoptosis, B-cel-differentiation, expression of protein and regulation of genes.
Results
Our results show that induction of NF-kappa B in the context of overexpression of c-Myc, i) by EBV latency III program, provides a selective advantage to those cells (gene expression in favor of a high metabolism, intense proliferation and protection against apoptosis), ii) by TLR9 (in vivo and in vitro model) increases the survival and proliferation of B lymphocytes of λ-c-Myc mice (increase of activated B cells, splenomegaly, increased B cells proliferation), and iii) by CD40 in the double transgenic CD40/Myc mice have a very aggressive B lymphomagenesis with in vivo increased proliferation and tumorigenesis.
Conclusion
We concluded that, whatever the tested model, NF-kappa B and c-Myc are functionally synergistic for transformation B cells.
Session topic: E-poster
Keyword(s): Lymphoma, Lymphomagenesis, MYC, NF- B
Abstract: E1382
Type: Eposter Presentation
Background
Not only Burkitt lymphoma (BL) with the translocation of MYC, but also diffuse large B-cell lymphoma (DLBCL) by other mechanisms (mutation, amplification, promoter dysregulation…) are associated with dysregulation of c-Myc, the master transcription factor for proliferation. DLBCL’s are classified in two subgroups: “Germinal center B-cell” (GCB) without and “activated B-cell” (ABC) with constitutive NF-kappa B activation. This constitutive activation of NF-kappa B can be the result of genetic alterations (MYD88, A20, TRAF2, and TRAF5) or the activation of B-cell receptor or CD40. These features raise the question of the synergy between NF-kappa B and c-Myc in ABC DLBCL. By inducing c-Myc and NF-kappa B, via in particular, the viral oncogene LMP1 (Latent Membrane Protein 1), Epstein-Barr virus (EBV) immortalized B cells are another example of the coexistence of these two transcription factors in continuous proliferating B-cells. Although BL are described without NF-kappa B activation, frequent association with EBV raises the question of the role of NF-kappa B activation during the early phase of the oncogenic process.
Aims
To study the synergy between NF-kappa B and c-Myc using the effect of several NF-kappa B drivers in the context of a continuous activation of c-Myc.
Methods
In vitro, study of an EBV and c-Myc double inducible human B-cell model and Burkitt lymphoma cell lines. Ex vivo and in vivo, study of TLR9 activation of B cells from the λ-c-Myc transgenic mouse model. In vivo, study of double transgenic mouse model with constitutive activation of CD40 and c-Myc (mouse CD40 / Myc). Techniques used are those for studying functional proliferation, apoptosis, B-cel-differentiation, expression of protein and regulation of genes.
Results
Our results show that induction of NF-kappa B in the context of overexpression of c-Myc, i) by EBV latency III program, provides a selective advantage to those cells (gene expression in favor of a high metabolism, intense proliferation and protection against apoptosis), ii) by TLR9 (in vivo and in vitro model) increases the survival and proliferation of B lymphocytes of λ-c-Myc mice (increase of activated B cells, splenomegaly, increased B cells proliferation), and iii) by CD40 in the double transgenic CD40/Myc mice have a very aggressive B lymphomagenesis with in vivo increased proliferation and tumorigenesis.
Conclusion
We concluded that, whatever the tested model, NF-kappa B and c-Myc are functionally synergistic for transformation B cells.
Session topic: E-poster
Keyword(s): Lymphoma, Lymphomagenesis, MYC, NF- B
Type: Eposter Presentation
Background
Not only Burkitt lymphoma (BL) with the translocation of MYC, but also diffuse large B-cell lymphoma (DLBCL) by other mechanisms (mutation, amplification, promoter dysregulation…) are associated with dysregulation of c-Myc, the master transcription factor for proliferation. DLBCL’s are classified in two subgroups: “Germinal center B-cell” (GCB) without and “activated B-cell” (ABC) with constitutive NF-kappa B activation. This constitutive activation of NF-kappa B can be the result of genetic alterations (MYD88, A20, TRAF2, and TRAF5) or the activation of B-cell receptor or CD40. These features raise the question of the synergy between NF-kappa B and c-Myc in ABC DLBCL. By inducing c-Myc and NF-kappa B, via in particular, the viral oncogene LMP1 (Latent Membrane Protein 1), Epstein-Barr virus (EBV) immortalized B cells are another example of the coexistence of these two transcription factors in continuous proliferating B-cells. Although BL are described without NF-kappa B activation, frequent association with EBV raises the question of the role of NF-kappa B activation during the early phase of the oncogenic process.
Aims
To study the synergy between NF-kappa B and c-Myc using the effect of several NF-kappa B drivers in the context of a continuous activation of c-Myc.
Methods
In vitro, study of an EBV and c-Myc double inducible human B-cell model and Burkitt lymphoma cell lines. Ex vivo and in vivo, study of TLR9 activation of B cells from the λ-c-Myc transgenic mouse model. In vivo, study of double transgenic mouse model with constitutive activation of CD40 and c-Myc (mouse CD40 / Myc). Techniques used are those for studying functional proliferation, apoptosis, B-cel-differentiation, expression of protein and regulation of genes.
Results
Our results show that induction of NF-kappa B in the context of overexpression of c-Myc, i) by EBV latency III program, provides a selective advantage to those cells (gene expression in favor of a high metabolism, intense proliferation and protection against apoptosis), ii) by TLR9 (in vivo and in vitro model) increases the survival and proliferation of B lymphocytes of λ-c-Myc mice (increase of activated B cells, splenomegaly, increased B cells proliferation), and iii) by CD40 in the double transgenic CD40/Myc mice have a very aggressive B lymphomagenesis with in vivo increased proliferation and tumorigenesis.
Conclusion
We concluded that, whatever the tested model, NF-kappa B and c-Myc are functionally synergistic for transformation B cells.
Session topic: E-poster
Keyword(s): Lymphoma, Lymphomagenesis, MYC, NF- B
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