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Leuk Res ; 38(1): 131-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24268349

ABSTRACT

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).


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Forkhead Transcription Factors/genetics , Leukemia, Myeloid/genetics , fms-Like Tyrosine Kinase 3/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Acute Disease , Adult , Blotting, Western , Cell Line, Tumor , Flow Cytometry , Forkhead Box Protein O1 , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Leukemic , HL-60 Cells , Humans , Leukemia, Myeloid/metabolism , Leukemia, Myeloid/pathology , Leukocyte Count , Mutation , Oligonucleotide Array Sequence Analysis , Prognosis , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Tandem Repeat Sequences , Transcriptome , fms-Like Tyrosine Kinase 3/metabolism
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