Personalised treatments for splenic marginal zone lymphoma
Splenic marginal zone lymphoma (SMZL) is a low grade B-cell lymphoma and patients with this lymphoma show remarkably variable clinical outcome. Although the majority of patients with SMZL present with an indolent clinical course, approximately 30% of cases show an aggressive presentation and die of the disease within 5 years of diagnosis. Currently, it is not possible to predict the clinical outcome of patients with SMZL upfront at diagnosis and stratify them for appropriate treatments. This is essentially hampered by a lack of characterisation of their genetics and molecular mechanisms underlying the lymphoma development. By sequencing the coding regions of the whole genome, we recently identified novel recurrent KLF2 mutations in SMZL, which encodes for a nuclear protein regulating gene expression. Subsequent validation study demonstrated that KLF2 mutation was the most frequent genetic change in SMZL and the mutation was significantly associated with several other recurrent genetic changes. In this grant application, we propose to further characterise the molecular actions of these genetic changes and decipher their molecular mechanisms underlying SMZL development. The knowledge learnt will help to develop novel therapeutic strategies and personalised treatments.