CircRNA study in MLL::AF4 rearranged acute lymphoblastic leukemia
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ABSTRACT:
PROVIDER: PRJNA883420 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
2008-11-04 | GSE12362 | GEO
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
2008-11-04 | GSE12360 | GEO
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
2008-11-04 | GSE12361 | GEO
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. Experiment Overall Design: Total RNA from normal pro-B, pre-B, immature B and mature B lymphocytes, and from leukemic pre-B cells was isolated and hybridized to Affymetrix expresison microarrays.
2008-11-13 | E-GEOD-12310 | biostudies-arrayexpress
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. This SuperSeries is composed of the SubSeries listed below.
2008-11-04 | GSE12363 | GEO
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. Keywords: Cell type comparison
2008-11-04 | GSE12310 | GEO
Project description:MLL/AF4 fusion transcript knock-down time course in the MLL/AF4-positive B-cell precursor ALL cell line SEM using MLL/AF4 fusion site-specific siRNAs (siMLL/AF4). The aim was to identify genes responsive to MLL/AF4 expression modulation.
2018-07-21 | GSE71140 | GEO
Project description:The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well-established that MLL-AF4 arises pre-natally during human development, its effects on hematopoietic development in utero remains unexplored. We have created a human-specific in vitro system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Differentiation and functional studies as well as clonal analyses and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. It enhances the specification of hemogenic precursors from hESCs and impairs further hematopoietic commitment of these precursors in favour of the endothelial cell fate. Similar to that reported in cord blood CD34+ hematopoietic stem/progenitor cells (HSPCs), MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells in vitro or in vivo, indicating that additional events may be required to initiate leukemogenesis or that embryonic hematopoiesis is not the appropriate human cellular target for MLL-AF4-mediated leukemogenesis. This work illustrates how hESCs can provide unique insights into human development and further our understanding of how leukemic fusion genes known to arise pre-natally regulate human embryonic hematopoietic specification. MLL is involved in transcriptional regulation and most MLL translocations appear to result in increased expression of Hox genes and hematopoietic genes. We therefore assessed the impact of MLL-AF4 expression on the transcriptome of hESCs. Gene expression profiling performed in MLL-AF4 hESCs revealed that MLL-AF4 preferentially activates transcription. 1826 out of the 3001 genes (61%) expressed were up-regulated in MLL-AF4 hESCs. Human ESC samples were collected during the exponential cell growth phase and stabilized in RNA later. 500 ng of each total RNA sample was labelled with Cy3 using the Quick-Amp Labelling kit and hybridized with the Gene Expression Hybridization kit to a Whole Human Genome Oligo Microarray (Agilent Technologies) following the Manufacturer’s instructions. Each cell line was analyzed as independent duplicates. NEO-expressing (empty lentivector) hESC line was used as the baseline.
2011-06-09 | E-GEOD-29869 | biostudies-arrayexpress
Project description:Infants diagnosed of precursor B-cell acute lymphoblastic leukemia (iB-ALL) presenting MLL-AF4 chromosomal rearrangement are at high risk of disease progression into fatal outcome. This specific subtype of pediatric leukemia constitutes a tough challenge in leukemia research, given the difficulties found when trying in vivo modelling. However, the understanding of mechanisms leading to proper lymphocyte generation may become of high utility in gaining deep insight on this malignancy. As we report here, the lack of HDAC7, a key transcriptional regulator in B lymphocyte differentiation, worsens the prognosis of iB-ALL patients. In fact, MLL-AF4+ iB-ALL patients with high expression of HDAC7 display an improved survival, partially mediated by the repression of oncogenes, such as c-MYC, and chemoresistance markers, like the ASNS enzyme. Accordingly, HDAC7 drastically reduces leukemic cells proliferation in MLL-AF4+ iB-ALL through the induction of apoptosis. Moreover, RNA sequencing of HDAC7-overexpressing cells has revealed that HDAC7 alters the genomic profiling of MLL-AF4+ iB-ALL cells towards that of healthy B-cell progenitors. In summary, the findings here reported highlight the role of HDAC7 in predicting prognosis of a lethal subtype of iB-ALL and open new clinical perspectives, since MLL-AF4+ iB-ALL infants would highly benefit from therapeutic options eventually restoring HDAC7 expression.
2021-06-04 | GSE151793 | GEO
Project description:In MLL-rearranged (MLLr) leukemias the N terminal part of the MLL gene can be fused to over 60 different partner genes. Here, we investigate the genome wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and their epigenetic signatures in order to define a core set of MLLr targets. We uncover both common as well as specific MLL-AF9 and MLL-AF4 target genes, which are all marked by H3K79me2, H3K27ac, and H3K4me3. Apart from promoter binding, we also identify MLL-AF9 and MLL-AF4 binding at specific subsets of non overlapping active distal regulatory elements. Despite this differential enhancer binding MLL-AF9 and MLL-AF4 still share a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34+ and monocyte specific genes. Comparing these datasets revealed several zinc finger transcription factors as potential MLL-AF9 co-regulators. Together these results suggest that MLL-fusions collaborate with specific subsets of TFs to aberrantly regulate the RUNX1 gene program in 11q23 AMLs.
2017-01-24 | GSE79899 | GEO