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

Claire H Seedhouse; Ken I Mills; Sophie Ahluwalia; Martin Grundy; Shili Shang; Alan K Burnett; Nigel H Russell; Monica Pallis

doi:10.1016/j.leukres.2013.10.030

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

Claire H Seedhouse, Ken I Mills, Sophie Ahluwalia, Martin Grundy, Shili Shang, Alan K Burnett, Nigel H Russell, Monica Pallis

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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).

Original language	English
Pages (from-to)	131-137
Journal	Leukemia research
Volume	38
Issue number	1
Early online date	07 Nov 2013
DOIs	https://doi.org/10.1016/j.leukres.2013.10.030
Publication status	Published - Jan 2014

Bibliographical note

ASJC Scopus subject areas

Oncology
Hematology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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).",

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year = "2014",

month = jan,

doi = "10.1016/j.leukres.2013.10.030",

language = "English",

volume = "38",

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journal = "Leukemia research",

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T1 - Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1

AU - Seedhouse, Claire H

AU - Mills, Ken I

AU - Ahluwalia, Sophie

AU - Grundy, Martin

AU - Shang, Shili

AU - Burnett, Alan K

AU - Russell, Nigel H

AU - Pallis, Monica

PY - 2014/1

Y1 - 2014/1

N2 - 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).

AB - 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).

U2 - 10.1016/j.leukres.2013.10.030

DO - 10.1016/j.leukres.2013.10.030

M3 - Article

C2 - 24268349

SN - 0145-2126

VL - 38

SP - 131

EP - 137

JO - Leukemia research

JF - Leukemia research

IS - 1

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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