Assessment of Blood Biomarkers by DNA Microarrays in Patients With Aggressive Lymphoma BMS_LyTrans
Condition: DLBCL
MeSH terms: Lymphoma; Aggression
Study type: Observational

Summary: 
      Diffuse Large B-cell Lymphoma (DLBCL) is the most frequent high grade lymphoma in adults.
      Although immunotherapy has improved its prognosis, DLBCL is a heterogeneous disease with
      patients exhibiting a wide range of outcomes with a 5-year overall survival ranging between
      55 to 94% depending of the International Prognostic Index factor. Diagnostic and prognostic
      biomarkers are mandatory to optimize treatment. Transcriptomics has been used to detect such
      new biomarkers using microarrays analyses applied to RNA collected from total tumor tissues
      or cell extracts. Molecular prognostic factors have been thoroughly studied in DLBCL tumor
      tissues. However, it is a big challenge to obtain transcriptomic-qualified tumor samples in a
      multicentric and prospective clinical trial. Coordinating nvestigator hypothesized that blood
      may be a deep source of native and secreted analytes and therefore carries transcriptomic
      signatures related to DLBCL and its prognosis. This project is organized in the extension of
      the GOELAMS-075 clinical trial which concerns aggressive DLBCL.
    

Detailed description: 
      Two complementary approaches will be followed, one at the transcriptomic level for
      confirmation of diagnostic biomarkers and to assess for predictive biomarkers. The other one
      concern biologic studies to validate our biomarkers at the tissue level. Our project will be
      organized around 4 workpackages (WP), each of them includes tasks with a specific schedule &
      predefined deliverables. The first one concerns the general management, data warehouse,
      collections and different administrative and preanalytic issues. The 3 other WPs are
      scientific. We are first going to validate a 30-gene list, candidate diagnostic biomarkers,
      by qRT-PCR on: *) an independent set of DLBCLs compared to matched healthy blood donors
      (sensitivity assessment) and, **) on a series of low tumor burden DLBCLs, mantle cell
      lymphomas and non-malignant inflammatory disease constituted by patients with a septic shock
      (specificity assessment). All this latter collections are already available and ready to use.
      Secondly, we will complete our series of 89 hybridized patients on AFFY WholeExon microarrays
      by 60 supplementary and available samples in order to assess for molecular predictor of
      patient outcome. This question will be address based on the 3-year and 5-year as well, EFS
      (Event Free Survivor). All the clinical data are available through the GOELAMS eCRF. Since we
      dispose of a 31 probesets, 30 single genes, signature for the DLBCL diagnosis that involves 9
      genes related to the myeloid compartment including 6 genes involved directly or not to the
      Myeloid-Derived Cell Suppression (MDSC) process, 20 genes described in the context of the
      cancer and, 11 genes connected to endothelial cells, we decided to explore by flow cytometry
      blood circulating cells. We will look for myeloid populations & subpopulations, endothelial
      cells and microparticles. The goal is the identification of specific MDSC perturbations,
      angiogenic abnormalities and functional impacts on the immune response in the context of the
      cancer.

      We expect by our work to drive both basic science and clinical implications. On the
      scientific level, blood carries molecular and cellular components involved in tumor-host
      interactions. Our project should bring a deeper understanding in the immunological response
      that takes place in the blood compartment. This immunological response will be characterized
      on a molecular, cellular and functional level. On a clinical point of view, it may bring a
      new prognostic model in DLBCL. As blood is easily accessible, we expect it to be easily
      implemented in clinical practice and to allow the design of new clinical trials stratified on
      tumor biology features. It may also become a new way to monitor DLBCL's response to
      treatment. Furthermore, this project will provide a large amount of molecular data that can
      be easily connected with other ongoing GOELAMS studies. Valorisation of our findings will
      also be serious issue since our project is highly original and valuable.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        DLBCL or Healthy blood donors or septic patient or GOELAMS 075 patients in completed
        remission
      
Biospecimen description: 
      For this study, 4 newly included cohorts are necesseray :

        -  100 new DLBCL patients are necessary. The blood will be taken at the diagnosis for DLBCL
           patients included 075-GOELAMS trial or 075-like patient.

        -  100 healthy blood donors. This cohort of matched for sex & gender will be constituted at
           the EFS (French Blood Bank) of Rennes.

        -  100 septic patients included at the Rennes University Hospital.

        -  100 075-like DLBCL patients in completed remission.

      This project will also used already available blood collections: 2) Mantle cell lymphoma, 3)
      localized DLBCL and septic shock. Paraffin blocks of patient 075-trial DLBCLs are in the
      GOELAMSthèque bank localized in the Pathology Department Hôtel Dieu, Paris supervised by Pr
      Diane Damotte. Tissue Microarrays and complete paraffin blocks as well as some -80° tumors
      are already available.
    
Keywords: Hematology; Secondary lymphoid organs