Hence, inhibiting EZH2 along with TKI therapy increases activation of H3K27me3 targets such as CDKN2A and upregulates pro-apoptotic targets of P53 (e.g., NOXA, P53 upregulated modulator of apoptosis (PUMA), BAX, CDKN2A, TNFRS10B), causing TKI sensitivity to be restored and CML LSCs to be eradicated [70, 213]. The gene discussed is CDKN2A; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.