Richter Syndrome
Conditions
Keywords
Richter Syndrome, Genomics, Proteomics, Chemotherapy resistance
Brief summary
Biological study on Richter Syndrome (RS), an agressive lymphoma that arises from Chronic Lymphocytice Leukemia (CLL). RS presents with the same histological aspect as primitive Diffuse Large B-Cell Lymphoma (DLBCL), but is associated with a poor prognosis, due to chemorefractoriness. This study aims at understanding the biological determinants of chemotherapy resistance in Richter Syndrome.
Detailed description
With the help of the French National Research Group on CLL (FILO / French Innovative Leukemia Organization), the investigators are currently gathering fresh frozen cell pellets at CLL stage, and lymph node biopsies at Richter stage. The investigators also gathered lymph node biopsies from DLBCL, as a reference group. The investigators will perform genomic and proteomic comparative studies between CLL and Richter, as well as between Richter and primitive DLBCL, to understand the biological determinants of clonal evolution and chemorefractoriness of Richter Syndrom.
Interventions
GENETICWhole exome sequencing.
Retrospective biological exploration of the samples, including tumoral DNA exploration.
GENETICRNA sequencing
Characterization of tumor transcriptomic profile.
OTHERMass spectrometry
Characterization of tumor proteomic profiles.
Sponsors
French Innovative Leukemia Organization (FILO)
Institut National de la Santé Et de la Recherche Médicale, France
Central Hospital, Nancy, France
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of a Diffuse Large B-Cell Lymphoma arising in the context of a Chronic Lymphocytic Leukemia (group 1) or diagnosis of a primitive Diffuse Large B-Cell Lymphoma (group 2), or diagnosis of a Diffuse Large B-Cell Lymphoma arising in a context of small cells lymphoma, excluding CLL (group 3), or benefit from a diagnostic lymph node biopsy that did not reveal any tumor involvment (primitive or metastatic) (group 4). * Patients must benefit from a lymph node biopsy at diagnosis. * Patients must be followed by a FILO (French Innovative Leukemia Organization) member * Histology of Diffuse Large B-Cell Lymphoma or Hodgkin histology. * Suitable clinical data available. * Samples must meet the following requirement :RIN (RNA Integrity Number) \> 5 et DIN (DNA Integrity Number) \> 6.5.
Exclusion criteria
• Samples that do not meet the inclusion criteria (insufficient clinical data, analysis impossible due to insufficient sample quality).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole exome sequencing data using next generation sequencing method | 3 years | Comparison between the DNA sequences from Richter syndrome samples and DNA sequences from primitive DLBCL samples to identify a set of mutations that are specific to Richter syndrome. For each position, the result is mutated or unmutated. |
| RNA sequencing data using next generation sequencing method | 3 years | Measurment of gene expression for all genes. Comparison of these expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of genes which expression levels are different in Richter samples compared primitive DLBCL and normal lymph nodes. Gene expression is a quatitative value. This set of genes forms a specific transcriptomic signature of Richter syndrome. |
| Proteomic analysis using mass spectrometry | 3 years | Mass spectrometry allows identification and measurment of the expression level of the 5,000 most expressed proteins in a sample. The investigators want to compare the protein expression levels between Richter samples, primitive DLBCL samples and normal lymph nodes to identifiy a set of proteins that are highly expressed in Richter samples (but not in primitive DLBCL or normal lymph nodes). This set of proteins forms a specific proteomic signature of Richter. Protein expression is a quatitative value expressed as an absolute number of copies in a cell. |
Countries
France
Contacts
Primary ContactJulien Broseus, MD, PhD
Backup ContactVéronique Saunier
Outcome results
None listed