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Identification of a common prognostic gene signature and its association with miR-181 regulation in human acute myeloid leukemia

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE30258: Identification of miR-181 target genes and a common prognostic gene signature in AML GSE30285: Identification of prognostic gene signatures in AML Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: chunjiang he

PROVIDER: E-GEOD-30257 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.

Li Zejuan Z Huang Hao H Li Yuanyuan Y Jiang Xi X Chen Ping P Arnovitz Stephen S Radmacher Michael D MD Maharry Kati K Elkahloun Abdel A Yang Xinan X He Chunjiang C He Miao M Zhang Zhiyu Z Dohner Konstanze K Neilly Mary Beth MB Price Colles C Lussier Yves A YA Zhang Yanming Y Larson Richard A RA Le Beau Michelle M MM Caligiuri Michael A MA Bullinger Lars L Valk Peter J M PJ Delwel Ruud R Lowenberg Bob B Liu Paul P PP Marcucci Guido G Bloomfield Clara D CD Rowley Janet D JD Chen Jianjun J

Blood 20120117 10

Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, ...[more]

PMID: 22251480

Similar Datasets

Identification of prognostic gene signatures in AML

Project description:Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially. In addition, this data set has also been used to identify a common prognostic gene signature in human AML (Li Z. et al., unpublished). 93 human AML samples bearing various cytogenetic and molecular abnormalities are used to identify miR-181 target genes and a common prognostic gene signature.

2012-04-03 | E-GEOD-30285 | biostudies-arrayexpress

Identification of miR-181 target genes and a common prognostic gene signature in AML

Project description:Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially. In addition, this data set has been used to identify a common prognostic gene signature (Li Z. et al. unpublished). 65 human AML samples bearing various cytogenetic and molecular abnormalities are used to identify miR-181 target genes and a common prognostic gene signature.

2012-04-03 | E-GEOD-30258 | biostudies-arrayexpress

Expression data from peripheral blood mononuclear cell in patients with type 1 diabetes before and after peripheral stem cell transplantation

Project description:Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approaches that can improve beta cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute response in peripheral blood genomic expression profiling at the six-month follow-up. Peripheral blood mononuclear of newly diagnosed type1 diabetes patients at diagnosis and at six months post-transplantation by autologous peripheral stem cell were purified by LymphoprepTm gradient purification according to the manufacturer's instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.

2012-02-20 | E-GEOD-29908 | biostudies-arrayexpress

Expression data from peripheral blood mononuclear cell in patients with type 1 diabetes compared with normal controls

Project description:Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells.Dys-regualtion of the component of peripheral blood mononuclear cells (PBMCs), including T-cells and B-cells, and smaller amounts of NK cells and dendritic cells, have all been implicated in this process This study sought to identify T1D associated differently expressed genes in the peripheral blood mononuclear cell (PBMC). Peripheral blood mononuclear of newly diagnosed type1 diabetes patients and normal controls were purified by LymphoprepTm gradient purification according to the manufacturer’s instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.

2014-08-16 | E-GEOD-55098 | biostudies-arrayexpress

microRNA expression data from peripheral blood mononuclear cell in patients with type 1 diabetes compared with normal controls.

Project description:Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic b cells. It has been reported that dys-regulation of microRNAs (miRNAs) may contribute to the pathogenesis of autoimmune diseases, including T1D. This study sought to identify T1D associated miRNAs in the peripheral blood mononuclear cell (PBMC). Peripheral blood mononuclear of newly diagnosed type1 diabetes patients and normal controls were purified by LymphoprepTm gradient purification according to the manufacturerM-bM-^@M-^Ys instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.

2014-08-16 | E-GEOD-55099 | biostudies-arrayexpress

Peripheral blood mononuclear cell in patients with type 1 diabetes compared with normal controls

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-16 | E-GEOD-55100 | biostudies-arrayexpress

Transcription signature of Multiple Sclerosis

Project description:This SuperSeries is composed of the following subset Series: GSE17393: Transcription signature of Multiple Sclerosis in peripheral blood mononuclear cells. GSE17409: Pregnancy changes expression in peripheral blood mononuclear cells of healthy donors GSE17410: Pregnancy changes expression in peripheral blood mononuclear cells of Multiple Sclerosis (MS) patients Refer to individual Series

2010-01-10 | E-GEOD-17449 | biostudies-arrayexpress

Pregnancy changes expression in peripheral blood mononuclear cells of healthy donors

Project description:Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a healthy donors signature comparing female healthy specimens before pregnancy with respect to female healthy specimens at ninth month pregnancy. Subjects were followed in the outpatients clinic and blood was collected before pregnancy and at the following time points during pregnancy: first trimester (gestational age at sampling 12 weeks), second trimester (24 weeks), and third trimester (36 weeks). Before-pregnancy samples were obtained in a treatment-free period and after anticonceptional drug withdrawal. Peripheral blood mononuclear cells (PBMCs) obtained from 11 women (7 healthy donors before pregnancy and 4 healthy donors at 9th month pregnancy) were analyzed by oligonucleotide microarray technology.

2010-01-09 | E-GEOD-17409 | biostudies-arrayexpress

Pregnancy changes expression in peripheral blood mononuclear cells of Multiple Sclerosis (MS) patients

Project description:Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female MS specimens before pregnancy with respect to female MS specimens at ninth month pregnancy. Subjects were followed in the outpatients clinic and blood was collected before pregnancy and at the following time points during pregnancy: first trimester (gestational age at sampling 12 weeks), second trimester (24 weeks), and third trimester (36 weeks). Before-pregnancy samples were obtained in a treatment-free period and after anticonceptional drug withdrawal. Peripheral blood mononuclear cells (PBMCs) obtained from 17 women (8 MS patients before pregnancy and 9 MS patients at 9th month pregnancy) were analyzed by oligonucleotide microarray technology.

2010-01-10 | E-GEOD-17410 | biostudies-arrayexpress

Transcription signature of Multiple Sclerosis in peripheral blood mononuclear cells.

Project description:Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female healthy specimens with respect to MS patients Subjects were followed in the outpatients clinic and blood was collected before pregnancy and at the following time points during pregnancy: first trimester (gestational age at sampling 12 weeks), second trimester (24 weeks), and third trimester (36 weeks). Before-pregnancy samples were obtained in a treatment-free period and after anticonceptional drug withdrawal. Peripheral blood mononuclear cells (PBMCs) obtained from 15 women (8 MS patients and 7 healthy controls) were analyzed by oligonucleotide microarray technology.

2010-01-10 | E-GEOD-17393 | biostudies-arrayexpress

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