Co-targeting leukemia-initiating cells and leukemia bulk leads to disease eradication

Co-targeting the plasticity and heterogeneity of cancer is fundamental to achieve and maintain complete remission (CR). We exploited murine models of acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia driven by the promyelocytic leukemia/retinoic acid receptor (PML-RARα) oncofusion protein, which recruits histone deacetylase (HDAC)-containing complexes. We investigated the effect of two HDAC inhibitors: valproic acid (VPA), and SAHA/vorinostat with all-trans retinoic acid (ATRA), on the bulk cells and LICs of two APLs with different LIC frequencies. VPA and SAHA selectively target the bulk APL cells and LICs respectively. VPA+SAHA+ATRA combination induced CR in an APL model with lower LIC frequency. Genome-wide transcriptomic analysis of two acute promyelocytic leukemic clones with different LIC frequencies