Chronic lymphocytic leukemia is characterized by the proliferation of B cells of the immune system. Although it is usually an indolent type of leukemia, 5% to 10% of patients eventually develop a more aggressive lymphoma with a poor prognosis. This process is called the Richter transformation.

Now, a Clínic-IDIBAPS team with the participation of IDIBELL has generated a mouse model that recreates this transformation and will allow the search for new treatments for these patients, who currently have few therapeutic options. The research group has shared all the details of this unique new model in the scientific journal Leukemia.

To generate this model, they injected cells from a patient with chronic lymphocytic leukemia into a mouse. This type of model is called patient-derived xenografts, and it is the first time a Richter transformation model is generated from cells of a patient with chronic lymphocytic leukemia, recapitulating what happens in the patient months later. According to the researchers, this discovery is a key tool for understanding this transformation and searching for new, more effective therapies.

A promising treatment

The molecular analyses that were possible thanks to this new model have revealed that, once Richter’s transformation has developed, lymphoma cells show high oxidative phosphorylation and low B-cell receptor signaling, which would explain the resistance to certain treatments that many patients develop.

Following these results, the researchers tested whether inhibition of oxidative phosphorylation could stop or slow the progression of lymphoma. The results, both in cultured cells and in a mouse model, are promising, as a significant reduction in the proliferation of tumor cells is shown.

This project has been funded by the Ministry of Science and Innovation, European Regional Development Funds, CERCA program, CIBERONC, Ministry of Universities, and the support of the American Association for Cancer Research, the European Hematology Association and the Lady Tata Memorial Trust.

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).