The fusion partner specifies the oncogenic potential of NUP98 fusion proteins

NUP98 is among the most promiscuously translocated genes in hematological diseases. Among the 28 known fusion partners, there are two categories: homeobox genes and non-homeobox genes. The homeobox fusion partners are well-studied in animal models, resulting in HoxA cluster overexpression and hematological disease. The non-homeobox fusion partners are less well studied. We created transgenic animal models for three NUP98 fusion genes (one homeobox, two non-homeobox), and show that in this system, the NUP98-homeobox fusion promotes self-renewal and aberrant gene expression to a significantly greater extent. We conclude that homeobox partners create more potent NUP98 fusion oncogenes than do non-homeobox partners

A fate worse than death: apoptosis as an oncogenic process

Apoptotic cell death is widely considered a positive process that both prevents and treats cancer. Although undoubtedly having a beneficial role, paradoxically, apoptosis can also cause unwanted effects that may even promote cancer. In this Opinion article we highlight some of the ways by which apoptosis can exert oncogenic functions. We argue that fully understanding this dark side will be required to optimally engage apoptosis, thereby maximizing tumour cell kill while minimizing unwanted pro-tumorigenic effects