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PMID: 24268349 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1.

Leukemia research ·Vol. 38 ·No. 1 ·2014-01-00 ·页码 131-7

Seedhouse CH, Mills KI, Ahluwalia S, Grundy M, Shang S, Burnett AK, Russell NH, Pallis M

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).

Keywords

ABCB1 AML FLT3-ITD FOXO1 p-glycoprotein

MeSH 主题词

ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics,metabolism Acute Disease Adult Blotting, Western Cell Line, Tumor Flow Cytometry Forkhead Box Protein O1 Forkhead Transcription Factors/genetics,metabolism Gene Expression Regulation, Leukemic HL-60 Cells Humans Leukemia, Myeloid/genetics,metabolism,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/genetics,metabolism

化学物质

ATP Binding Cassette Transporter, Subfamily B, Member 1 FOXO1 protein, human Forkhead Box Protein O1 Forkhead Transcription Factors FLT3 protein, human fms-Like Tyrosine Kinase 3

作者与单位

共 8 位作者，点击展开单位 / ORCID

Seedhouse Claire H

Department of Haematology, University of Nottingham, Nottingham, UK. Electronic address: [email protected].

Mills Ken I

Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, UK.

Ahluwalia Sophie

Department of Haematology, University of Nottingham, Nottingham, UK.

Grundy Martin

Department of Haematology, University of Nottingham, Nottingham, UK; Clinical Haematology, Nottingham University Hospitals, Nottingham, UK.

Shang Shili

Department of Haematology, University of Nottingham, Nottingham, UK.

Burnett Alan K

Department of Haematology, Cardiff University, Cardiff, UK.

Russell Nigel H

Department of Haematology, University of Nottingham, Nottingham, UK; Clinical Haematology, Nottingham University Hospitals, Nottingham, UK.

Pallis Monica

Clinical Haematology, Nottingham University Hospitals, Nottingham, UK.

Article Info

Journal

Leukemia research

Abbr.

Leuk Res

ISSN

1873-5835

DOI

10.1016/j.leukres.2013.10.030

Corresponding email

[email protected]

Published

2014-01-00

电子出版

2013-00-08

页码

131-7

Language

English

Country/Region

England

NLM ID

7706787

External Links

PubMed source DOI: 10.1016/j.leukres.2013.10.030 View journal details

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Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1.

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