Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA_seq Analysis of Murine Leukemias for Identifying Potential Leukemia Fusion Targets and JAK1 regulated genes

ABSTRACT: Purpose: The goals of this study are to compare transcriptomes after shutting off the CALM-AF10, MLL-AF10 and MLL-AF9 fusion proteins in mouse AML cells. Furthermore, we also perform transcriptomic experiments to assess the changes in transcripts upon JAK1 deletion in mouse CALM-AF10 AML. Methods: Mouse AMLs cells grown in Mouse leukemia medium (see below) were treated with DMSO (Tet-On) or 4ug/ul Doxycycline (Tet-Off) and RNA was isolated to perform RNA-seq. RNA for CALM-AF10, MLL-AF10 was poly-A selected and MLL-AF9, total RNA was used to make RNAseq libraries using the NEB RNAseq lbrary prep kit. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the mouse genome (build mm9) and 60 million reads for MLL-AF9 data. Data analysis with BWA and TopHat workflows revealed genes that are significantly changed after shutting off the fusions or after deleting Jak1 in CALM-AF10 Jak1 floxed cells using the Cre recombinase. Conclusions:

ORGANISM(S): Mus musculus

PROVIDER: GSE164181 | GEO | 2021/01/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CRISPR Screening for CALM-AF10 interactome and transcriptional targets

Project description:We performed pooled CRISPR screens to determine the whether the CALM-AF10 target genes and protein interactors identified by RNA-Seq and proteomics methods are functional dependencies for CALM-AF10-driven AML. We constructed a pooled CRISPR library of CALM-AF10 mouse target genes and interactors, and used it to transduce CALM-AF10 mouse AMLs. The cells were sampled at "Day 0" and kept in culture to determine in vitro dependencies at day 12. For in vivo screens, the input cell pool from day 0 was injected in mice and mice where sacrificed upon signs of AML disease, and the AML cells were harvested.

2021-01-05 | GSE164183 | GEO

Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (mRNA)

Project description:The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion.

2011-10-05 | GSE27513 | GEO

Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (miRNA)

2011-10-05 | GSE27512 | GEO

CALM-AF10 T-ALL

Project description:Comparison of a series of 6 CALM-AF10 positive T-ALL to a series of 17 CALM-AF10 negative T-ALL Keywords: ordered

2005-07-01 | GSE2117 | GEO

Tissue and differentiation stage specific expression of CALM/AF10 is required for leukemogenesis

Project description:The translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.

2017-06-19 | GSE58853 | GEO

Expression Profiling of a CALM/AF10 leukemia mouse model

Project description:Expression profiling of three cell populations of a CALM/AF10 leukemia mouse model Keywords: expression profiling

2006-07-20 | GSE5030 | GEO

Genome wide mapping of histone 3 lysine 79 mono, di and trimethylation and histone 3 lysine 27 trimethylation in LSKs, GMPs and retroviral MLL-AF9 driven murine leukemias

Project description:We report the genome wide distribution of the three states of H3K79 methylation (H3K79me1/me2/me3) and H3K27me3 in mouse lineage negative Sca-1 positive Kit positive cells (LSKs), granulocyte macrophage progenitors (GMPs) and LSK derived MLL-AF9 leukemias in the presence or absence of the Af10 OM-LZ domain. Legend- MIT:MSCV-IRES-tdTomato (Empty vector control) and CRE (MIT vector with the Cre recombinase). We examined the H3K79 me1,me2,me3 and H3K27me3 profiles by ChIP-seq in lineage negative Sca-1 positive, Kit positive (LSK) cells, granulocyte macrophage progenitors (GMPs) and bone marrow cells from sacrificed terminally ill secondary MLL-AF9 positive leukemic mice. In case of the MLL-AF9 leukemias, the ChIP-seq experiments were performed in 2 conditions in the presence or absence of the Dot1l interacing octapeptide-motif leucine zipper (OM-LZ) domain of Af10. For the leukemia experiments, leukemias derived from the Af10 OM-LZ homozygous floxed background were transduced with MSCV-IRES-tdTomato control vector (MIT) or its Cre-recombinase expressing counterparts (CRE). Subsequently, we sorted tdTomato positive cells and injected them into sub-lethally irradiated syngenic secondary recipient mice. Seconday leukemias obtained from these MIT or CRE expressing cells were used for ChIP -seq studies.

2014-09-08 | E-GEOD-55038 | biostudies-arrayexpress

Transcription profiling of human CALM-AF10 positive and negative T-ALL samples

Project description:Comparison of a series of 6 CALM-AF10 positive T-ALL to a series of 17 CALM-AF10 negative T-ALL

2007-08-30 | E-GEOD-2117 | biostudies-arrayexpress

Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (miRNA)

2011-10-04 | E-GEOD-27512 | biostudies-arrayexpress

Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (mRNA)

2011-10-04 | E-GEOD-27513 | biostudies-arrayexpress