Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression of HOXB genes is significantly different in acute myeloid leukemia with a partial tandem duplication of MLL vs. a MLL translocation: a cross-laboratory study

ABSTRACT: In acute myeloid leukemia (AML), the mixed lineage leukemia (MLL) gene may be rearranged to generate a partial tandem duplication (PTD), or fused to partner genes through a chromosomal translocation (tMLL). In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other studies enriches samples for analysis and yields more conclusive results.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15013 | GEO | 2011/06/30

SECONDARY ACCESSION(S): PRJNA114729

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

MLL-PTD and RUNX1-knockout cooperate to induce MDS phenotypes

Project description:The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1α in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1αFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1α expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1∆/∆ with or without HIF-1α abrogation.

2018-12-23 | GSE86953 | GEO

H3K4me3 ChIP-Seq analysis of LSKs isolated from WT and Mll-PTD knock-in heterozygous mice

Project description:The MLL-PTD mutation is found in patients with MDS and AML, and not in other haematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice present with several MDS-associated features, such as increased self-renewal and apoptosis in HSPCs, expansion of the myeloid progenitor population, ineffective haematopoiesis, and skewed myeloid differentiation. MLL is an epigenetic regulator: its C-terminal Su[var]3–9, enhancer of zeste, trithorax (SET) domain has methyltransferase activity on lysine 4 on histone 3 (H3K4), which is retained in the MLL-PTD mutant. To clarify the effects of MLL-PTD on target gene regulation, we performed H3K4me3 ChIP-Seq analysis of LSKs isolated from WT and Mll-PTD knock-in heterozygous mice.

2018-12-01 | GSE75608 | GEO

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Project description:In this work we dissect the functional role of the HOXB-AS3 long non coding RNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 was found to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

2019-10-16 | PXD015520 | Pride

The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

2019-10-15 | GSE137851 | GEO

HOXB-AS3 expressions promote cell proliferation

Project description:We knock down HOXB-AS3 with shRNA in OCI/AML3 cell line to investigate the downstream pathways of HOXB-AS3 in the cell proliferation.

2019-07-16 | GSE114823 | GEO

POLR2M-mediated paused transcription silences tumor suppressor MIR139 in MLL-AF9 AML

Project description:MIR139 is a critical tumor suppressor and commonly silenced in human cancer, including acute myeloid leukemia (AML). Here, we found that depletion of identified MIR139 targets affects AML outgrowth. We unraveled the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. Epigenetic analyses revealed two well-conserved putative enhancer regions in close proximity of transcriptional start sites (TSS) of MIR139. These regions were silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these regions abolished MIR139 transcriptional regulation in normal and oncogenic conditions. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139-silencing factor. Furthermore, direct POLR2M binding to the MIR139 TSS induced paused transcription, which was abrogated upon PRC2 inhibition. We present evidence for an oncogenic POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. Together, our findings highlight the importance of POLR2M-mediated paused transcription in AML.

2021-11-11 | PXD022488 | Pride

MLL rearrangements in pediatric ALL and AML: MLL specific and lineage specific signatures

Project description:Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements. Gene expression signatures of acute lymphoblastic and myeloblastic leukemia samples with and without MLL rearrangements were analyzed using paired supervised analyses.

2009-07-22 | GSE14062 | GEO

An enhancer cluster promotes NPCs formation from ESCs through maintaining HoxB activation by long-range chromatin interaction

Project description:Homeobox B cluster genes (HoxB) are important marker genes for neural progenitor cells (NPCs) formation from embryonic stem cells (ESCs). However, mechanisms of HoxB activation in NPCs remain largely unknown. Here, we find an enhancer cluster (EnC) interacting with the HoxB locus by PLAC-seq analysis. CRISPR/Cas9-mediated EnC deletion significantly inhibited HoxB expression, indicating that the EnC is required for HoxB activation in NPCs. Transcriptome analysis revealed that differentiation-related master control genes and NPCs formation-related signaling pathways were significantly inhibited suggesting that the EnC is essential for NPCs formation. In summary, our results reveal a new mechanism about HoxB activation depending on EnC is crucial for NPCs formation.

2020-10-13 | GSE159378 | GEO

Analysis of AML/MDS patients with 11q/MLL amplification

Project description:AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, a later onset and fast progression of the disease with extremely poor prognosis. We and others have shown that the MLL gene is overexpressed in amplified cases; however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification. By means of array CGH performed in 12 patients we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases (GSE10258) were used to define candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of loss of 5q and 17p and expression of genes present in 11q23-25. Furthermore, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from several other types of AML, thus, indicating specific pathogenesis present in this entity. Keywords: comparative genomic hybridization; array CGH In this study, aCGH analysis performed on 12 DNA samples derived from patients with AML, preselected for the presence of MLL amplifications, were analysed on a submegabase resolution BAC array. No replicates, no dye swap was done. Gene expression profiling performed for 15 AML patients (GSE10258).

2008-06-30 | E-GEOD-9928 | biostudies-arrayexpress

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data