Understanding MYC driven aggressive B-cell lymphomas: pathogenesis and classification
Cet article passe en revue les perspectives offertes par les connaissances sur le rôle du gène Myc dans les lymphomes à grandes cellules B pour le diagnostic de la maladie et la prise en charge des patients
MYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC upregulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1. Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its pro-apoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. On the other hand, MYC protein upregulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review we integrate all this new information and discuss its perspectives, challenges and open questions for the diagnosis and management of the patients.
Blood , résumé, 2013