Stromal Cell Contribution to Human Follicular Lymphoma Pathogenesis

Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment

Expression Map of the Human Exome in CD34+ Cells and Blood Cells: Increased Alternative Splicing in Cell Motility and Immune Response Genes

International audienceBACKGROUND: Hematopoietic cells are endowed with very specific biological functions, including cell motility and immune response. These specific functions are dramatically altered during hematopoietic cell differentiation, whereby undifferentiated hematopoietic stem and progenitor cells (HSPC) residing in bone marrow differentiate into platelets, red blood cells and immune cells that exit into the blood stream and eventually move into lymphoid organs or inflamed tissues. The contribution of alternative splicing (AS) to these functions has long been minimized due to incomplete knowledge on AS events in hematopoietic cells. PRINCIPAL FINDINGS: Using Human Exon ST 1.0 microarrays, the entire exome expression profile of immature CD34+ HSPC and mature whole blood cells was mapped, compared to a collection of solid tissues and made freely available as an online exome expression atlas (Amazonia Exon! : http://amazonia.transcriptome.eu/exon.php). At a whole transcript level, HSPC strongly expressed EREG and the pluripotency marker DPPA4. Using a differential splicing index scheme (dsi), a list of 849 transcripts differentially expressed between hematopoietic cells and solid tissues was computed, that included NEDD9 and CD74. Some of these genes also underwent alternative splicing events during hematopoietic differentiation, such as INPP4B, PTPLA or COMMD6, with varied contribution of CD3+ T cells, CD19+ B cells, CD14+ or CD15+ myelomonocytic populations. Strikingly, these genes were significantly enriched for genes involved in cell motility, cell adhesion, response to wounding and immune processes. CONCLUSION: The relevance and the precision provided by this exon expression map highlights the contribution of alternative splicing to key feature of blood cells differentiation and function

Integrating clinical, gene expression, protein expression and preanalytical data for in silico cancer research.

International audienceWe present the phase I development of an integrative platform for the analysis of clinical, gene expression, protein expression and pre-analytical data. The platform is aimed at providing transparent access and analysis tools to researchers investigating new biomarkers and prognosis factors in the particular field of lymphoma diseases. In this article, we report on the data integration phase. The platform's principal advantage is its completeness as it integrates in a single environment clinical, genomic and proteomic data, allowing for their combined analysis. The architecture consists in a data warehouse including data on patients, clinical trials and array platforms and a DeMilitarized Zone for data exchange. A secure web-based platform allows any collaborative team to request the data warehouse and access basic statistics on integrated data. The presented system is currently in use

Lymphome B diffus à grandes cellules de morphologie anaplasique

International audienceLes lymphomes B diffus de morphologie anaplasique sont des entités remarquables appartenant à la catégorie des lymphomes B diffus à grandes cellules et non à celle des lymphomes anaplasiques. Leurs caractéristiques histologiques sont celles d'une tumeur à cellules pléomorphes, nécessitant d'éliminer différents diagnostics comme celui d'une métastase d'un mélanome, d'une tumeur germinale ou encore d'un sarcome. Nous rapportons ici le cas d'une patiente de 64 ans ayant présenté une atteinte ganglionnaire aortico-cave en insistant sur les caractéristiques histologiques et immunohistochimiques de ce lymphome

Les enjeux du préanalytique dans l’analyse du transcriptome et du proteome sanguins

De nombreux paramètres liés au patient et aux conditions de prélèvement d’un échantillon biologique peuvent influer sur les propriétés de cet échantillon. Ces paramètres préanalytiques sont particulièrement importants à maîtriser dans le contexte d’études cliniques multicentriques. Nous rapportons ici les résultats préliminaires d’une étude conduite par le groupe coopératif GOELAMS (Groupe Ouest-Est des Leucémies aiguës et Autres Maladies du Sang) afin d’identifier les paramètres préanalytiques susceptibles d’affecter une étude protéomique sur sérum dans le contexte d’études cliniques concernant les lymphomes B non hodgkiniens

Capacity of myeloid and plasmacytoid dendritic cells especially at mature stage to express and secrete HLA-G molecules

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Integrative Analysis of Cell Crosstalk within Follicular Lymphoma Cell Niche: Towards a Definition of the FL Supportive Synapse

International audienceFollicular lymphoma (FL), the most frequent indolent non-Hodgkin's B cell lymphoma, is considered as a prototypical centrocyte-derived lymphoma, dependent on a specific microenvironment mimicking the normal germinal center (GC). In agreement, several FL genetic alterations affect the crosstalk between malignant B cells and surrounding cells, including stromal cells and follicular helper T cells (Tfh). In our study, we sought to deconvolute this complex FL supportive synapse by comparing the transcriptomic profiles of GC B cells, Tfh, and stromal cells, isolated from normal versus FL tissues, in order to identify tumor-specific pathways. In particular, we highlighted a high expression of <i>IL-6</i> and <i>IL-7</i> in FL B cells that could favor the activation of FL Tfh overexpressing IFNG, able in turn to stimulate FL B cells without triggering MHC (major histocompatibility) class II expression. Moreover, the glycoprotein clusterin was found up-regulated in FL stromal cells and could promote FL B cell adhesion. Finally, besides its expression on Tfh, CD200 was found overexpressed on tumor B cells and could contribute to the induction of the immunosuppressive enzyme indoleamine-2,3 dioxygenase by CD200R-expressing dendritic cells. Altogether our findings led us to outline the contribution of major signals provided by the FL microenvironment and their interactions with malignant FL B cells

High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis.

International audienceFollicular lymphoma (FL) is characterized by the balanced chromosomal translocation t(14;18)(q32;q21) in about 80-90% of the cases. This primary event is not sufficient for emergence of FL, and acquisition of secondary genetic alterations is necessary to full disease manifestation