Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome

Richter syndrome (RS) represents the development of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), in the context of chronic lymphocytic leukaemia (CLL). At least two types of RS exist: (i) transformation of CLL into a clonally related DLBCL, that accounts for ~80% of cases; and (ii) development of a DLBCL unrelated to the CLL clone. Clonally related RS and clonally unrelated RS are distinct disorders (Rossi et al, 2011a). Clinically, transformation into a clonally related RS is frequently lethal with an expected survival of a few months, while CLL patients developing a clonally unrelated RS display a survival probability in the range of de novo DLBCL (Rossi et al, 2011a). Biologically, clonally related RS frequently acquire genetic lesions of TP53, MYC and NOTCH1, which are otherwise absent or exceptional in clonally unrelated RS (Rossi et al, 2011a).