Belver Lab – Leukemia and Immuno-Oncology
RESEARCH
Juvenile Myelomonocytic Leukemia (JMML)
Juvenile Myelomonocytic Leukemia (JMML) is a pediatric myeloproliferative neoplasm characterized by the constitutive activation of the RAS signaling pathway. This activation is driven in 90% of cases by germline or somatic mutations in the genes PTPN11, NRAS, KRAS, NF1, or CBL. Most JMML patients experience an aggressive clinical course of the disease, necessitating hematopoietic stem cell transplantation (HSCT) as the only curative treatment. Despite the progress made in recent years in the genetic characterization of JMML, this disease remains a clinical challenge due to its heterogeneity, difficult diagnosis, poor prognosis, and the lack of alternative treatment options beyond HSCT.
B-Cell Lymphoma
Chronic infections, particularly those involving viruses like Epstein-Barr and HIV, have been shown to intricately contribute to B-cell lymphoma initiation and progression. These infections disrupt B-cell homeostasis, fostering conditions favorable for lymphomagenesis by inducing genetic alterations, promoting cell proliferation, and inhibiting apoptosis. The resulting chronic inflammation further supports oncogenic transformation, contributing to genetic instability and activating pathways sustaining malignant B-cell growth. Comprehending this intricate interplay is imperative for the development of targeted therapies and preventive measures specific to B-cell lymphoma.
Systemic Lupus Erythematosus (SLE)
The standard of care for SLE has been traditionally based on the use of non-specific anti inflammatory and immunomodulatory/immunosuppressive agents. Although these therapies significantly improve disease symptoms, they are associated with a broad range of short- and long- term adverse effects and their efficacy remains suboptimal in controlling lupus-related flares.
Persistent disease activity together with accumulative treatment associated toxicities increase the risk of irreversible damage accrual and reduced survival in SLE patients. This speaks to the urgent need of developing new therapeutic interventions that target specific molecular mechanisms involved in the pathogenesis of the disease and provide higher efficiency and safety for SLE treatment.
