CDK6 loss in steady-state conditions does not significantly affect the distribution of LSK populations (top panel). Stress conditions will result in a rapid exit from G₀ of HSCs as a result of a CDK6-dependent transcriptional repression of Egr1. Loss of CDK6 prevents the repression of Egr1 to allow cells to exit G₀. In leukemia models in which CDK6 is aberrantly activated, the exit of LSCs from the G₀ phase depends on CDK6. CDK6 loss results in failure of the leukemogenesis process (bottom panel). 5-FU, 5-fluorouracil; poly(I:C), polyinosinic:polycytidylic acid.