As the genetic alteration is not expressed in the bulk of the B committed tumoral cells, ETV6-RUNX1 is acting as a “hit and run” oncogene that primes the cell-of-origin (HS/PC) to a B cell program preleukemic clone that due to a second hit (exposure to infection) is fully transformed into a leukemic cell (Figure 1). Here, ETV6 is linked to infection.