Oncogenetic landscape of lymphoma in patients with IEI

Lay summary of project 

Inborn errors of immunity (IEI) constitute a heterogeneous group of diseases predisposing individuals to lymphoproliferative disorders, that range from polyclonal lymphoproliferation to overt mature lymphoma. Lymphoma can severely compromise patients’ prognosis and still represent a therapeutic challenge in the context of IEI. Moreover, lymphoma may be the first manifestation of an underlying IEI that has not been previously diagnosed. Developing tools to predict the presence of IEI, along with identifying genetic variants predisposing to lymphoma, are crucial for optimizing patient care.

Lymphomagenesis in IEIs relies on constitutional genetic defects such as DNA repair abnormalities, apoptosis defects, or tumor immunosurveillance deficiencies. Other mechanisms, including oncogenic viruses like Epstein-Barr virus (EBV), chronic inflammation, or homeostatic dysregulation, are implicated. Lymphomagenesis in IEIs is also likely characterized by fewer somatic mutations and reduced genetic heterogeneity compared to immunocompetent individuals. However, the biology of lymphoma cells in the IEI setting remains poorly understood.

This pilot initiative aims to establish a comprehensive platform by analyzing a cohort of IEI-related lymphomas from the French national IEI reference center registry (CEREDIH), using an integrative pan-omics approach. We will also compare the molecular signatures of lymphoma associated with well-known IEI subtypes to those found in a matched cohort of immunocompetent adults. This original approach aims to identify novel tumor biomarkers indicative of underlying IEI and uncover key pathways that could serve as targets for personalized therapies.

Brief biography 

• Hematologist, Assistant-professor, Department of Adult Hematology, University Hospital Necker Enfants-Malades, Paris, France.
• Specialist in diagnosis and treatment of mature lymphoid cell malignancies. 
• Expertise in treatment of adult patients with inborn errors of immunity (IEI) and hematological manifestations (lymphoproliferations, lymphoma, cytopenia, etc)
• Local principal investigator clinical trials for lymphoma
• In charge of hematologists' education at Université de Paris Cité
• Member of the European Society for Immunodeficiencies (ESID). Active member of the French national reference center for IEI (CEREDIH). Member of the French LYmphoma Study Association (LYSA), active member of the LySA working groups for T-cell lymphoma and chair for the mantle cell lymphoma working group. Member of the scientific committee of the European Mantle Cell Lymphoma Network (EMCL). 

Interest in both rare lymphomas (Mantle cell lymphoma, T-cell lymphoma) and inborn errors of immunity (IEI). These two themes often overlap, since lymphoproliferative diseases are common complications of IEI, and cover rare pathologies that are often unrecognized. Past and current research projects all have a translational focus. Some have thus made it possible to develop diagnostic and therapeutic tools in mantle cell lymphoma and rare T-cell lymphomas. Others aim to discuss the indications and the place of specific treatments such as allogeneic stem-cell transplantation in adult with IEI or innovative treatments in lymphomas. Finally, I am leading research projects on lymphoma that occurred in patients with IEI and on high-risk Mantle cell lymphoma.