In conclusion, we propose that (a) hnRNP K is a negative regulator of promyelocytic differentiation in APL by maintaining the stability of PML‐RARα, (b) this contributes positively to cell survival and maintenance through regulation of c‐Myc, Bcl‐xL, and SET proteins, (c) ERK signaling is essential for leukemogenesis and viability, by regulating hnRNP K protein (demonstrated by the treatment with U0126), and (d) hnRNP K and SET are regulating PU.1 expression/levels. The gene discussed is BCL2L1; the disease is acute promyelocytic leukemia.