RARA and acute myeloid leukemia: The observation that mutations in signaling pathways proteins frequently co-occur with chromosomal rearrangements in hematopoietic transcription factors (PML-RARA, CBFβ-MYH11, RUNX1-RUNX1T1) led to the hypothesis that AML results from the cooperation of mutations that confer a proliferative advantage (class I mutations) with mutations that induce a block in differentiation (class II mutations), the 2-hit model [1].