CDK4 and neoplasm: Indeed our most recent genome-wide CRISPR-Cas9 knockout screening identified and validated Erk1/2 as a CRBN-IKZF1/3 axis-independent modulator of BM-milieu-induced sensitivity to iMiDs; based on our current study, ERK1/2i + CDK4/6i may also overcome this mechanism of IMiD induced resistance in the tumor BM microenvironment [63].