ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/029/SRR26171929/SRR26171929_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/035/SRR26171935/SRR26171935_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/033/SRR26171933/SRR26171933_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/027/SRR26171927/SRR26171927_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/029/SRR26171929/SRR26171929_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/027/SRR26171927/SRR26171927_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/030/SRR26171930/SRR26171930_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/031/SRR26171931/SRR26171931_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/034/SRR26171934/SRR26171934_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/033/SRR26171933/SRR26171933_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/032/SRR26171932/SRR26171932_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/028/SRR26171928/SRR26171928_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/030/SRR26171930/SRR26171930_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/026/SRR26171926/SRR26171926_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/032/SRR26171932/SRR26171932_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/035/SRR26171935/SRR26171935_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/028/SRR26171928/SRR26171928_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/034/SRR26171934/SRR26171934_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/031/SRR26171931/SRR26171931_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR261/026/SRR26171926/SRR26171926_2.fastq.gzprimaryOK200GenomicsBC Children's Hospital Research Institutehttps://www.ebi.ac.uk/ena/browser/view/PRJNA1020909Mus musculusxref:PubMed:37824841Common infections have long been proposed to play a role in the development of pediatric B cell acute lymphoblastic leukemia (B-ALL). However, epidemiological studies report contradictory effects of infection exposure on subsequent B-ALL risk, and no specific pathogen has been definitively linked to the disease. A unifying mechanism to explain the divergent outcomes could inform disease prevention strategies. We previously reported that the pattern recognition receptor (PRR) ligand Poly(I:C) exerted effects on B-ALL cells that were distinct from those observed with other nucleic acid-based PRR ligands. Here, using multiple double-stranded RNA moieties, we show that the overall outcome of exposure to Poly(I:C) reflects the balance of opposing responses induced by its ligation to endosomal and cytoplasmic receptors. This PRR response biology is shared between mouse and human B-ALL and increases leukemia-initiating cell burden in vivo during the preleukemia phase of B-ALL, primarily through TNF-a signaling. The age of the responding immune system further influences the impact of dsRNA exposure on B-ALL cells in both mouse and human settings. Overall, our study demonstrates that potentially pro- and anti-leukemic effects can each be generated by stimulation of pathogen recognition pathways and indicates a mechanistic explanation for the contrasting epidemiologic associations reported for infection exposure and B-ALL. Overall design: To investigate the effect of Poly (A:U) on LICs, Eμ-Ret pups were treated with either PBS or Poly(A:U) and LICs were purified 7 days later. RNA-seq was performed on purified LICs from 5 PBS treated and 5 Poly (A:U) treated , Eμ-Ret pups.ENAfalseAge and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B cell precursor populations.Age and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B cell precursor populations.2025-09-242023-12-15PRJNA1020909GSE2440181009037824841