Metabolism in cancer and aging.
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults and represents a heterogeneous group of tumors with distinct subtypes that differ in genetic alterations, clinical outcome, response to treatment and prognosis. Approximately 5-15% of DLBCL are high grade B cell lymphomas (HGBL) with rearrangements of MYC and BCL2 and they are known as “double-hit” lymphoma (DHL) or “triple hit lymphoma” (THL) if they also present BCL6 translocations. Due to simultaneous activation of these driver oncogenes, DHLs are among the most aggressive and chemoresistant lymphoma subtype with minimal treatment options and have poor outcomes. Furthermore, the co-expression of MYC and BCL2 proteins without underlying rearrangements is considered a new adverse prognostic indicator termed double-expressor lymphoma (DEL). Deregulated MYC expression contributes to metabolic reprogramming in tumor cells through a complex network of factors. Specifically, c-MYC-transformed lymphoma B cells rely on glutamine metabolism for bioenergetics and redox homeostasis. In addition, serine metabolism, through the enhanced activity of SHMT2 enzyme, contributes to the biology of MYC-aggressive lymphomas. However, the metabolic features of the HGBL-DH lymphomas are not fully understood and could imply potentially targetable vulnerabilities. Understanding the unique biology of these tumors, including metabolism, could provide a rationale for exploring targeted agents beyond the current focus on BCL2 and MYC inhibitors.
Our lab, aims to characterize the metabolic features of these particular tumors using transcriptomic and metabololomic tools in preclinical models and patient samples, and screen new metabolic vulnerabilities that could be used as new targeted therapies for these aggressive lymphomas with very poor outcomes with the standard therapies.
Ana Ortega Molina.
Correo electrónico: aortega@cbm.csic.es.
Centro de Biología Molecular Severo Ochoa (CBM).
Número de plazas ofertadas: 1.
Facultad de Medicina. Universidad Autónoma de Madrid. Calle del Arzobispo Morcillo 4. 28029 Madrid. Tel.: +34 914 975 486. Correo electrónico: informacion.medicina@uam.es
