Leukemia and immuno-oncology
Belver’s Lab

The Leukemia and Immuno-Oncology group focuses its work on two main research lines. On the one hand, the group studies the molecular mechanisms driving oncogenic transformation and progression in Juvenile Myelomonocytic Leukemia (JMML) with the aim of identifying therapeutic targets that can potentially translate into new treatments for these patients. On the other hand, our team is also interested in studying the impact of human papillomavirus (HPV) infection in the development of B-cell lymphoma.

Molecular pathways and targeted therapies in JMML

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of early childhood for which hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment. One out of three children diagnosed with JMML succumb to disease. And these numbers are even more dramatic for those patients carrying activating mutations in the PTPN11 gene, which present the most aggressive forms of the disease with a survival rate of only 25%.

JMML presents a low mutational burden in the coding genome, with five canonical mutations in RAS pathway genes (PTPN11, KRAS, NRAS, CBL and NF1) that act as drivers in more than 90% of the patients and only a few described secondary mutations. However, this apparently simple genetic landscape is accompanied by a high phenotypical variability within the patients, which cannot be explained by our current knowledge. Thus, JMML is still an important clinical challenge due to its heterogeneity, difficult diagnosis, poor prognosis, and the lack of alternative treatment options other than HSCT.

To shed light on these questions, our group has set two main goals:

1. To identify potential functional aberrations in JMML non-coding regulatory elements that can contribute to the pathogenesis of the disease and explain its heterogeneity.
2. To develop new small-molecule compounds that block the oncogenic effects of PTPN11 mutations as a therapeutic alternative for the treatment of aggressive JMML.

Role of HPV in B-cell lymphoma pathogenesis

HPV infections are the most common sexually transmitted diseases, affecting approximately 80% of all men and women during their lifetime. Interestingly, HPV has been associated to an increased B-cell lymphoma incidence. Moreover, some studies have shown evidence of HPV infection in B-cell lymphoma cells, suggesting that HPV-driven oncogenic effects might directly contribute to B-cell transformation. However, the specific role of HPV in lymphomagenesis remains unknown. The aim of this project is to shed light on the mechanisms underlying the association between HPV and B-cell lymphoma.