Itchy mast cells in MPNs.

tions. It is tempting to speculate that these cases are linked by a common underlying mutation that predisposes to DNA replication errors. What “unlinks” WT1 and NPM1 are their different prognostic influences. This study makes it clear that WT1 mutations are associated with unfavorable outcomes in childhood AML, as shown in the figure. Another important difference between WT1 and NPM1 mutations is that WT1 mutations retain prognostic significance in the presence of FLT3/ITD. While the favorable influence of NPM1 mutations appears to be “trumped” by FLT3/ITD, this study suggests that the unfavorable influence of FLT3/ITD may be “trumped” by wild-type WT1, since the outcome for FLT3/ITD patients who lacked WT1 mutations was not significantly worse than for patients with wild-type FLT3. What this study lacks is evidence supporting a causative link between WT1 mutations and the comparatively poor response to therapy. Of particular interest would be evidence at a functional cellular level that WT1 mutational status is associated with parameters that might predict for poor clinical outcome, such as in vitro chemoresistance or differences in apoptotic responses to DNA damage. Such findings might pave the way for WT1 mutations to serve not only as prognostic markers but as potential molecular targets for novel antileukemic therapies. Conflict-of-interest disclosure: The author declares no competing financial interests. ■