Unknown,Transcriptomics,Genomics,Proteomics

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Remodeling of the DNA methylation landscape of CD34+ cells from fetal liver / cord blood upon upon CRISPR mediated t(4:11) rearrangements.


ABSTRACT: The prognosis of infant B-cell acute lymphoblastic leukemia (iB-ALL) remains dismal, especially in patients harboring the MLL-AF4 (KTM2A-AFF1) rearrangement, which arises prenatally in early hematopoietic stem/progenitor cells (HSPCs). MLL-AF4+ B-ALL shows a bimodal localization of the MLL gene breakpoint within the MLL break cluster region, and two subgroups of patients based on the gene expression pattern of the HOXA/MEIS cluster have been identified. The pathogenic mechanisms in MLL-AF4+ B-ALL are challenging to study functionally due to the absence of faithful human cellular models recapitulating the disease phenotype and latency. Here, we assess the molecular contribution and leukemogenic capacity of MLL breakpoints occurring in either intron 10 (MLLi10, centromeric) or intron 12 (MLLi12, telomeric) in ontogenically-different human HSPCs sourced prenatally (fetal liver) and neonatally (cord blood). CRISPR-Cas9-induced MLL-AF4 (MA) targeting either MLLi10 (Mi10A) or MLLi12 (Mi12A) causes MA-driven in vitro myeloid immortalization in both fetal liver- and cord blood-CD34+ HSPCs. The cellular ontogeny and the location of the MLL breakpoint influenced the capacity of MLL-edited CD34+ HSPCs to initiate pro-B-ALL in vivo, which faithfully recapitulated the molecular, transcriptomic and methylome profiles of patients with primary MA+ iB-ALL. This dataset contains the DNA methylation information (Illumina MethylationEPIC Beadchip platform) of MLL-edited CD34+ cells (i10 or i12). BCPs, used as controls, were obtained from E-MTAB-8505

ORGANISM(S): Homo sapiens

SUBMITTER: Mario Fraga F. 

PROVIDER: E-MTAB-12806 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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