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Catherine Henry - One of the best experts on this subject based on the ideXlab platform.

  • pan hdac inhibitors restore prdm1 response to il21 in crebbp mutated Follicular Lymphoma
    Clinical Cancer Research, 2019
    Co-Authors: Fabienne Desmots, Celine Pangault, Francisco Llamasgutierrez, Cedric Pastoret, Jerome Le Priol, Valerie Camaraclayette, Gersende Caron, E Guiheneuf, Mikael Roussel, Catherine Henry
    Abstract:

    Purpose: Follicular Lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with Follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of Follicular Lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either Follicular Lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, Follicular Lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the Follicular Lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In Follicular Lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these Follicular Lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with Follicular Lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of Follicular Lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with Follicular Lymphoma through the induction of the expression of plasma cell genes.

Fabienne Desmots - One of the best experts on this subject based on the ideXlab platform.

  • pan hdac inhibitors restore prdm1 response to il21 in crebbp mutated Follicular Lymphoma
    Clinical Cancer Research, 2019
    Co-Authors: Fabienne Desmots, Celine Pangault, Francisco Llamasgutierrez, Cedric Pastoret, Jerome Le Priol, Valerie Camaraclayette, Gersende Caron, E Guiheneuf, Mikael Roussel, Catherine Henry
    Abstract:

    Purpose: Follicular Lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with Follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of Follicular Lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either Follicular Lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, Follicular Lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the Follicular Lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In Follicular Lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these Follicular Lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with Follicular Lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of Follicular Lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with Follicular Lymphoma through the induction of the expression of plasma cell genes.

Mikael Roussel - One of the best experts on this subject based on the ideXlab platform.

  • pan hdac inhibitors restore prdm1 response to il21 in crebbp mutated Follicular Lymphoma
    Clinical Cancer Research, 2019
    Co-Authors: Fabienne Desmots, Celine Pangault, Francisco Llamasgutierrez, Cedric Pastoret, Jerome Le Priol, Valerie Camaraclayette, Gersende Caron, E Guiheneuf, Mikael Roussel, Catherine Henry
    Abstract:

    Purpose: Follicular Lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with Follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of Follicular Lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either Follicular Lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, Follicular Lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the Follicular Lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In Follicular Lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these Follicular Lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with Follicular Lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of Follicular Lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with Follicular Lymphoma through the induction of the expression of plasma cell genes.

E Guiheneuf - One of the best experts on this subject based on the ideXlab platform.

  • pan hdac inhibitors restore prdm1 response to il21 in crebbp mutated Follicular Lymphoma
    Clinical Cancer Research, 2019
    Co-Authors: Fabienne Desmots, Celine Pangault, Francisco Llamasgutierrez, Cedric Pastoret, Jerome Le Priol, Valerie Camaraclayette, Gersende Caron, E Guiheneuf, Mikael Roussel, Catherine Henry
    Abstract:

    Purpose: Follicular Lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with Follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of Follicular Lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either Follicular Lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, Follicular Lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the Follicular Lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In Follicular Lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these Follicular Lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with Follicular Lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of Follicular Lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with Follicular Lymphoma through the induction of the expression of plasma cell genes.

Gersende Caron - One of the best experts on this subject based on the ideXlab platform.

  • pan hdac inhibitors restore prdm1 response to il21 in crebbp mutated Follicular Lymphoma
    Clinical Cancer Research, 2019
    Co-Authors: Fabienne Desmots, Celine Pangault, Francisco Llamasgutierrez, Cedric Pastoret, Jerome Le Priol, Valerie Camaraclayette, Gersende Caron, E Guiheneuf, Mikael Roussel, Catherine Henry
    Abstract:

    Purpose: Follicular Lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with Follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of Follicular Lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either Follicular Lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, Follicular Lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the Follicular Lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In Follicular Lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these Follicular Lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with Follicular Lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of Follicular Lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with Follicular Lymphoma through the induction of the expression of plasma cell genes.