Regulation of ABCB1 (P-glycoprotein/Pgp) in AML was investigated. In a historical cohort with Pgp and transcriptional regulator expression profiling data available (n = 141), FOXO1 correlated with Pgp protein expression. This was confirmed in an independent cohort (n = 204). Down-regulation (siRNA) or hyperactivation (nicotinamide) of FOXO1 led to corresponding changes in Pgp. Low FOXO1 expression correlated with FLT3-ITDs (p < 0.001) and siRNA inhibition of FLT3-ITD up-regulated FOXO1. As FOXO1 is a key growth regulator, it may underpin biological differences between Pgp-positive clones (low WBC and primary resistant disease) and clones with a FLT3-ITD (associated with a high WBC and early relapse).
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ASJC Scopus subject areas
- Cancer Research