SPI1 and cancer: For instance, deletion of an upstream regulatory element causes down-regulation of PU.1 expression and leads to AML development.[52] In contrast, RUNX1 levels are increased in many cancers, especially in AML.[53] Interestingly, both up- and down-regulation of the transcription factor GATA2 can promote leukemogenesis.[54–58] These findings exemplify the strong impact that transcription factor imbalance can have on proliferation, differentiation, and death of hematopoietic progenitor cells.