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Analysis of gene expression changes in MLL-rearranged leukaemia cell lines with induced resistance against CCI-006

ABSTRACT: Analysis of gene expression changes in MLL-rearranged leukaemia cell lines with induced resistance against CCI-006

PROVIDER: PRJNA476064 | ENA |

REPOSITORIES: ENA

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Analysis of gene expression changes in MLL-rearranged leukaemia cell lines with induced resistance against CCI-006

Project description:Gene expression analysis of two MLL-r leukaemia cell lines (SM6p2 and SM6p3) and the parental PER-485 MLL-rearranged leukaemia cell line they were derived from by continuous culturing in CCI-006. SM6p2 and SM6p3 thereby developed induced resistance against the compound. The aim of this experiment was to identify any gene expression changes in SM6p2 and SM6p3 cells induced by continuous culturing in CCI-006, thereby potentially providing insight into the mechanisms of primary and induced resistance of MLL-rearranged leukaemia cell lines against the cytotoxic compound CCI-006.

2019-06-01 | GSE115794 | GEO

Gene expression analysis of a MLL-rearranged leukaemia cell line, PER-485, treated with small molecule CCI-006.

Project description:A phenotypic cell-based high-throughput screen identified a novel small molecule, CCI-006 with selective cytotoxic activity against MLL-rearranged leukaemia cell lines. The aim of this experiment was to identify the mechanism of action of CCI-006 by investigating the gene expression changes induced in a MLL-rearranged leukaemia cell line following a short incubation with the compound.

2019-06-01 | GSE115793 | GEO

Gene expression analysis of a MLL-rearranged leukaemia cell line, PER-485, treated with small molecule CCI-006.

Project description:Gene expression analysis of a MLL-rearranged leukaemia cell line, PER-485, treated with small molecule CCI-006.

| PRJNA476065 | ENA

Analysis of changes in gene expression upon CCI-006 treatment and resistance development of the MLL-rearranged leukaemia cell line PER-485

Project description:Analysis of changes in gene expression upon CCI-006 treatment and resistance development of the MLL-rearranged leukaemia cell line PER-485

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Proteome alterations in MLL-rearranged leukemia cells following WIN Site inhibition

Project description:WIN Site inhibitors bind the WIN Site of WDR5 resulting in decreased transcription of WDR5 target genes, many of which encode components of the protein synthesis machinery. In this study, we determined proteome alterations in an MLL-rearranged leukemia cell line treated for either 24 or 72 hours with a WIN Site inhibitor. The data from these studies, along with Ribo-Seq, RNA-Seq, and CRISPR screen experiments, guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.

2023-07-04 | PXD035129 | Pride

Quantitative cellular proteome analysis of Fetal- and Adult-Derived MLL-Rearranged Leukemia

Project description:Infant and adult MLL-rearranged (MLLr) leukemia represents a disease with few treatment options and a dismal prognosis. Here, we present an in-depth proteomic characterization of in utero-initiated and adult-onset MLLr leukemia in a mouse model of MLL-ENL-mediated leukemogenesis. We characterize early proteomic events of MLL-ENL-mediated transformation in fetal and adult progenitors.

2024-04-02 | PXD042249 | Pride

Tet1 plays an essential oncogenic role in MLL-rearranged leukemia

Project description:TET1, the founding member of the TET family of enzymes (TET1/2/3) that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), was first identified as a partner gene in MLL-rearranged leukemia, but its definitive pathological role in leukemia is unclear. The down-regulation of all three TET genes and loss-of-function mutations of TET2 have been frequently observed in various cancers, and it was thought that they all play tumor-suppressor roles in tumorigenesis. Here we show that TET1 is likely a direct target of MLL and significantly up-regulated in MLL-rearranged leukemia, associated with an increased level of 5hmC. Our further in vitro and in vivo studies demonstrate that Tet1 plays an indispensable oncogenic role in MLL-rearranged leukemia, through cooperating with MLL fusion proteins in regulating their co-targets including the Hoxa/Meis1/Pbx3/Flt3 genes. Our data delineate a MLL-fusion/Tet1/Hoxa/Meis1/Pbx3/Flt3 signaling axis in MLL-rearranged leukemia, and highlight TET1 as a potential therapeutic target in treating this presently therapy-resistant disease. We report genome-wide 5hmC enrichment profiles and RNA-Seq gene expression in MLL-AF9 transformed and control mouse bone marrow mononuclear cells. These 5hmC profiles are derived from selctive chemical labeling and enrichment of 5hmC containing genomic DNA fragments, while the RNA-Seq expression profiles are generated from polyA enriched RNA

2015-12-14 | E-GEOD-42990 | biostudies-arrayexpress

Foetal-specific contributors to infant MLL-AF4-driven Acute Lymphoblastic Leukaemia

Project description:As MLL-rearranged infant leukaemia is known to initiate in utero, we sought to identify developemntal genes expressed in foetal cells that may aid leukaemogenesis. Bulk RNA-Seq was therefore carried out on mouse and human foetal liver blood progenitors (lymphoid-primed multipotent progenitors [LMPPs] and haematopoietic stem cells/ multipotent progenitor cells [HSC/MPPs]) and compared with the same cell types isolated from developmentally later human cord blood and mouse adult bone marrow.

2021-10-07 | GSE167234 | GEO

MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia

Project description:In this study, we identify MBNL1 as a unique molecular vulnerability across MLL-rearranged leukemias. Through transcriptomic profiling and novel splicing analyses of MLL-rearranged leukemia cell lines following shRNA knockdown of MBNL1, we show that MBNL1 regulates alternative splicing (predominantly intron retention) of genes essential to MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.

2020-03-25 | GSE123441 | GEO

shRNA profiling of human MLL cells reveals HOXA9 is required for survival in human MLL rearranged acute leukemias

Project description:Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biological characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias utilizing RNAi. Gene expression profiling after HOXA9 suppression demonstrated co-downregulation of a program highly expressed in human MLL-AML (this study) and murine MLL-leukemia (Krivtsov et al. 2006) stem cells including HOXA10, MEIS1, PBX3 and MEF2C. Our data indicates an important role for HOXA9 in human MLL-rearranged leukemias, and suggests targeting HOXA9 or downstream programs may be a novel therapeutic option. Experiment Overall Design: RNA was purified from t(9;11) MOLM-14 AML cells 44h after transduction in triplicates with 2 of the two most effective HOXA9shRNA constructs (3 x 1F3-HOXA9shRNA; 3 x 2A5-HOXA9shRNA) or GFP-controlshRNA (6x).

2009-01-26 | E-GEOD-13714 | biostudies-arrayexpress

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