Infection exposure promotes ETV6-RUNX1 precursor B cell leukemia revealing secondary genomic alterations in histone modification genes
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ABSTRACT: We used microarrays to investigate gene expression changes in ETV6/RUNX1 proB and preB cells Bone marrow proB and preB cells of four ETV6/RUNX1 mice compared with bone marrow proB and preB cells of three WT mice and three Pax5+/- mice.
Project description:ATAC-seq of pre-proB, proB and preB populations from Ergfl/fl bone marrow, pre-proB cell population from Rag1CreT/+;ErgΔ/Δ bone marrow, and pre-proB, proB and preB populations from from Rag1CreT/+;ErgΔ/Δ;IgHVH10tar bone marrow.
Project description:RNA-seq of pre-proB, proB and preB populations from Ergfl/fl bone marrow, pre-proB cell population from Rag1CreT/+;ErgΔ/Δ bone marrow
Project description:ProB-PreB, immature and mature B cells were sorted from the bone marrow of mice and the RNA subsequently sequenced. The mice were all Mb1-Cre +/- and either Vhl flox/flox or VHL flox/WT
Project description:We studied the role of the stable Igh mRNA in Igh chain check point. Here we generated RNA-seq data from sorted ProB (CD19+B220+c-Kit+CD25-) and PreB (CD19+B220+c-Kit-CD25+) populations from Bone marrow of mice.
Project description:Arrested bone marrow (BM) lymphoid cell differentiation underlies the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). Recurrent genetic lesions often directly involve transcription factors (TFs), such as ETV6 and RUNX1 found in the most common ALL translocation.
Project description:ETV6-RUNX1 is a first-hit mutation in childhood B cell precursor acute lymphoblastic leukaemia. ETV6-RUNX1 is a fusion protein which inherits the DNA-binding runt domain from RUNX1. Here we performed chromatin precipitation for native RUNX1 and ETV6-RUNX1 using RUNX1 antibodies and specifically for the ETV6-RUNX1 fusion using a V5-tag pull down.
Project description:Arrested bone marrow (BM) lymphoid cell differentiation underlies the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). Recurrent genetic lesions often directly involve transcription factors (TFs), such as ETV6 and RUNX1 found in the most common ALL translocation. Here, we studied differential gene expression in ETV6-RUNX1 primary ALL samples and the REH cell line using single cell RNA-seq (scRNA-seq). Submitter declares that the raw data will be deposited in EGA due to patient privacy concerns. The raw data can be accessed at https://www.ebi.ac.uk/ega/studies/EGAS00001004374
Project description:The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q), and +16 as possible early events in the leukemogenic process. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 23 leukemic bone marrow samples and one ETV6/RUNX1-positive cell line.
Project description:Analysis of gene signatures in WT+Ctrl vs WT+ETV6-RUNX1, Btg1-/- and Btg1-/-+ETV6-RUNX1 in cKit+Ter119- fetal liver-derived hematopoietic progenitor cells (FL-HPCs). The Btg1-/-+ETV6-RUNX1 FL-HPCs display a strong increase in proliferation compared to WT+ETV6-RUNX1. Total RNA otained from WT+Ctrl, WT+ETV6-RUNX1, Btg1-/-+Ctrl and Btg1-/-+ETV6-RUNX1 FL-HPCs cells that were cultured for 12 days in expansion medium.