T-ALL clonal dynamics and MSI2. (A) Two patterns of clonal evolution in response to treatment were identified in T-ALL. In clonal shift, there is substantial reshuffling of clonal composition after treatment, whereas in clonal drift no major clonal alterations occur, with most variation from diagnosis to relapse occurring at the transcriptional level. (B) Analysis of clonal drift resulted in the identification of a MSI2-MYC axis driving T-ALL relapse that can be counteracted by small molecule inhibition of MSI2. mRNA, messenger RNA. Illustration by Marta B. Fernandes.