Use of BCL7A as molecular target for DLBCL drug screening & development.

Diffuse large B-cell lymphoma is the most common type of Non-Hodgkin's Lymphomas (NHL). With an annual incidence of more than 100,000 cases worldwide, it is noted for its high aggressiveness and heterogeneity, both clinical and genetic, which limits the existence of effective treatment. Although more than half of these patients can achieve long-term remission, it remains a challenging clinical problem with approximately one-third of patients not being cured by standard immunochemotherapy regimens.

Among its molecular subtypes predominate the germinal center B cells (GCB) and the activated B cell variety (ACB), both characterized by their different gene expression profiles. The recent application of massive sequencing in this field has revealed mutation patterns that differ according to cell origin.

Researchers from the University of Granada and the Foundation for Biosanitary Research of Eastern Andalusia (FIBAO) have shown for the first time the tumor suppressing role of the BCL7A gene and the functional impact that some of its genetic variations have on the development of DLBCL.

Genetic mutations mapped in exon 1 and intron 1 splicing sites of the BCL7A gene have been identified mostly in DLBCL patients with the GCB subtype. Such mutations cause the loss of the amino-terminal domain of BCL7A, resulting in a truncated protein.

The present technology provides the use of BCL7A and the detection of its expression products to offer a novel tool for the treatment of DLBCL in terms of drug detection, prognosis, diagnosis and treatment.

ADVANTAGES AND BENEFITS:

• Diagnosis of the disease based on BCL7A mutations.These mutations are more frequent in diffuse large B-cell lymphomas (DLBCL), and more specifically in the specific germinal center subtype (GCB).
• Mutations are concentrated in a specific region of the BCL7A gene (first exon and splicing donor of intron 1) and occur exclusively somatically in tumors, making the analysis of tumor cells easier.
• In vitro and in vivo evidence.Restoration of BCL7A correlates with a tumor suppressor effect. These mutations abrogate the ability of BCL7A to bind to the SWI / SNF complex to perform its function.
• BCL7A expression levels are used to classify patients according to their prognosis.
• New tool for the development of new epigenetic drugs against cancer that targets histone marks with greater precision than previous generations.
• No specific equipment is necessary.The detection of the expression products of BCL7A can be carried out by a great variety of techniques, generally common and accessible in laboratories of the sector.
• Simple method.The possibility of using a kit or device makes it easier to obtain data to diagnose and predict this type of lymphoma.

ADDITIONAL REFERENCES:

Carlos Baliñas-Gavira, María Isabel Rodríguez, Álvaro Andrades, Marta Cuadros, Juan Carlos Álvarez-Pérez, Ángel F. Álvarez-Prado, Virginia G. de Yébenes, Sabina Sánchez-Hernández, Elvira Fernández-Vigo, Javier Muñoz, Francisco Martín, Almudena R. Ramiro, José Ángel Martínez-Climent and Medina PP. Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia 2020

Desired business relationship

Patent licensing

Applications

DLBCL diagnosis

Drug screening