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Genome-wide analysis of gene expression in MLL translocation transformed mouse leukemia cell lines

ABSTRACT: The purpose of this study is to investigate the transcriptional programs as it relates to disease latency initiated by different MLL fusion proteins, including: MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 and MLL-ENL. Leukemia cell lines were established by transforming kit+ mouse bone marrow cells with retroviruses coding MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 or MLL-ENL. At early phase after the cell lines were established, cells growing at exponential phase (cell density at 0.5~1x106/ml) were harvested for RNA extraction and sequencing purpose. Sequencing is performed on total RNA isolated from mouse leukemia cell lines generated from kit+ mouse bone marrow cells transduced with various MLL fusion proteins and is compared to control total RNA isolated from kit+ mouse bone marrow cells.

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Muntean

PROVIDER: E-GEOD-73457 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia.

Chen Lili L Sun Yuqing Y Wang Jingya J Jiang Hui H Muntean Andrew G AG

Oncotarget 20160501 18

MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs. RNA-sequencing and pathw ...[more]

PMID: 27007052

Similar Datasets

Genome-wide analysis of gene expression in MLL translocation transformed mouse leukemia cell lines

Project description:The purpose of this study is to investigate the transcriptional programs as it relates to disease latency initiated by different MLL fusion proteins, including: MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 and MLL-ENL. Leukemia cell lines were established by transforming kit+ mouse bone marrow cells with retroviruses coding MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 or MLL-ENL. At early phase after the cell lines were established, cells growing at exponential phase (cell density at 0.5~1x106/ml) were harvested for RNA extraction and sequencing purpose.

2016-07-07 | GSE73457 | GEO

Protein Interactions of 7 MLL-fusion Proteins

Project description:MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL protein. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins: MLL-AF1p, MLL-AF4, MLL-AF9, MLL-CBP, MLL-EEN, MLL-ENL and MLL-GAS7.

2018-05-25 | PXD009338 | Pride

Genome wide mapping of histone 3 lysine 79 dimethylation in MLL-AF6 murine leukemias

Project description:We report the genome wide distribution of H3K79 dimethylation in mouse MLL-AF6 positive leukemias to assess whether this epigenetic mark drives MLL-target gene expression. Examination of H3K79 dimethylation in bone marrow cells from sacrificed terminally ill MLL-AF6 positive leukemic mice. The retroviral MSCV-IRES-neo-MLL-AF6 construct was transduced into mouse bone marrow lineage negative Kit +, Sca + (LSK) cells and these cells were injected after G418 selection into irradiated syngenic mice to establish MLL-AF6 positive leukemias.

2013-04-03 | E-GEOD-43062 | biostudies-arrayexpress

Expression data from MLL-AF6 positive leukemia cells

Project description:The MLL gene on chromosome 11 fuses to the AF6 gene on chromosome 6 in a balanced chromosomal translocation that is characetristic of certain adult and pediatric human leukemias. We established a murine leukemia model of MLL-AF6 using the retroviral MLL-AF6 contruct in a bone marrow transplantation system. Leukemic bone marrow cells from a sacrificed moribund mouse were thawed and RNA was extracted using TRIZOL (Invitrogen) and purified further using the RNAeasy kit (Qiagen) under standard conditions and and hybridized onto Affymetrix arrays.

2013-04-03 | E-GEOD-43067 | biostudies-arrayexpress

Zinc finger protein 521 overexpression is a feature of MLL-rearranged acute myeloid leukemia and contributes to the maintenance of myeloid differentiation block

Project description:ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. In this study, we show that ZNF521 is significantly upregulated in MLL translocated AML patients from a large pediatric cohort, regardless of the type of MLL translocations such as MLL-AF9, MLL-ENL, MLL-AF10 and MLL-AF6 fusion genes. Our in vitro functional studies demonstrate that ZNF521 play a critical role in the maintenance of the undifferentiated state of MLL-rearranged cells. Furthermore, analysis of the ZNF521 gene promoter region shows that ZNF521 is a direct downstream target of both MLL-AF9 and MLL-ENL fusion proteins. Gene expression profiling of MLL-AF9-rearranged THP-1 cells after depletion of ZNF521 reveals correlation with several expression signatures including stem cell-like and MLL fusion dependent programs. These data suggest that MLL fusion proteins activate ZNF521 expression to maintain the undifferentiated state and contribute to leukemogenesis. ZNF521 is required to block differentiation in MLL-rearranged AML cells

2017-03-31 | GSE79110 | GEO

MLL partner genes confer distinct biological and clinical signatures of pediatric AML, an AIEOP study

Project description:We retrospectively analyzed AML patients enrolled in the AIEOP since 2000, 42 patients with 11q23 rearrangement were analyzed by gene expression profile Gene expression analyses were performed to compare AML MLL partner genes (AF9, AF10, AF6, ENL, ELL, Septin 6, and AF1q) Keywords: Expression data Class comparison between different AML MLL partner genes

2011-04-21 | E-GEOD-19577 | biostudies-arrayexpress

MLL partner genes confer distinct biological and clinical signatures of pediatric AML, an AIEOP study

2011-04-21 | GSE19577 | GEO

Expression data from conditionally immortalized MLL-AF9 and MLL-ENL hematopoietic progenitor cells following loss of MLL-fusion oncogene

Project description:Chromosomal translocations encoding the MLL-AF9 and MLL-ENL fusion transcription factors are prevalent in infant acute leukaemia and therapy-related leukaemia. In order to conditionally express the MLL-fusion oncogene in primary haematopoietic progenitor cells (HPC), retroviral delivery of the Tet-off expression system was used (Horton et al., Cancer Res, 2005). Treatment of the conditional cells with Doxycycline caused a decrease in MLL-AF9/ENL mRNA and protein expression, and resulted in terminal differentiation of the cells. By analysing global changes in gene expression after treatment of cells with Doxycycline we were able to identify a number of potential transcriptional target genes of the MLL-AF9 and MLL-ENL fusion oncogenes.

2014-12-01 | GSE59236 | GEO

RNA-Seq of human AML samples, and human cells transformed with MLL-ENL or MLL-AF6

Project description:RNA-Seq of 1) human AML samples; 2) sorted, uncultured distinct population from human cord blood (CB); 3) short-term (ST) cultured sorted CB cells transduced with MLL-ENL, MLL-AF6 or untransduced; and 4) cultured (LT) sorted CB cells transformed with MLL-ENL or MLL-AF6. Cells from MLL-fusion AML patients are bulk. Several cords were used for the sorting (CB1, CB2, CB3, 135, 141...) and these represent biological replicates. Several samples were sequenced several times in different lanes and results were merged together for the analysis (rep1,rep2...). Samples were used to determine the different effect of MLL-fusions in different celltypes just after the transduction, and after a longer time period when cells were transformed. Sorted CB samples, uncultured as well as transformed by MLL-fusions, were used in machine learning approach to predict which of the patients originated from which cell-type of origin.

2021-01-31 | E-MTAB-5501 | biostudies-arrayexpress

Runx1 deficiency effect on MLL-ENL cells

Project description:To identify the target genes of Runx1 in MLL fusion leukemia, we performed microarray analysis using control and Runx1-deficient MLL-ENL leukemia cells. Runx1 intact and excised bone marrow cells were transduced with MLL-ENL and transplanted into congenic mice. Leukemic cells were harvested from moribund mice, and gene expression was compared using 3 independent leukemia cells for each genotype.

2013-06-30 | E-GEOD-47402 | biostudies-arrayexpress

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