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Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia

ABSTRACT: Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia

PROVIDER: PRJNA1120376 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29293550.fastq.gz	Fastqsanger.gz
	SRR29293551.fastq.gz	Fastqsanger.gz
	SRR29293552.fastq.gz	Fastqsanger.gz
	SRR29293553.fastq.gz	Fastqsanger.gz
	SRR29293554.fastq.gz	Fastqsanger.gz

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Similar Datasets

Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia

Project description:Epidemiological studies report opposing influences of infection on childhood B cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus as a model early-life infection, we show that virus exposure within one week of birth induces profound depletion of transplanted B-ALL cells in two mouse models and of in situ-generated PLC in Eu-ret mice. The age_x0002_dependent depletion of PLC results from an elevated STAT4-mediated cytokine response in neonates, with high levels of IL-12p40-driven IFN-g production inducing PLC death. Similar PLC depletion can be achieved in adult mice by impairing viral clearance. These findings provide mechanistic support for an inhibitory effect of early-life infection on B-ALL progression and could inform development of therapeutic or preventative approaches.

2024-07-01 | GSE269131 | GEO

Proteogenomics of High hyperdiploid childhood acute lymphoblastic leukemia

Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.

2019-02-25 | PXD010175 | Pride

Proteogenomics of High hyperdiploid childhood acute lymphoblastic leukemia

Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.

2020-01-29 | MSV000084862 | MassIVE

Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia.

Project description:AbstractEpidemiological studies report opposing influences of infection on childhood B-cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus (CMV) infection as a model early-life infection, we show that virus exposure within 1 week of birth induces profound depletion of transplanted E2A-PBX1 and hyperdiploid B-ALL cells in wild-type recipients and in situ-generated PLC in Eμ-ret mice. The age-dependent depletion of PLC results from an elevated STAT4-mediated cytokine response in neonates, with high levels of interleukin (IL)-12p40-driven interferon (IFN)-γ production inducing PLC death. Similar PLC depletion can be achieved in adult mice by impairing viral clearance. These findings provide mechanistic support for potential inhibitory effects of early-life infection on B-ALL progression and could inform novel therapeutic or preventive strategies.

| S-EPMC11375503 | biostudies-literature

The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia

Project description:The presence of supernumerary chromosomes is the only abnormality shared by all patients diagnosed with high-hyperdiploid B cell acute lymphoblastic leukemia (HD-ALL). Despite being the most frequently diagnosed pediatric leukemia, the lack of clonal molecular lesions and complete absence of appropriate experimental models have impeded the elucidation of HD-ALL leukemogenesis. Here, we report that for 23 leukemia samples isolated from moribund Eμ-Ret mice, all were characterized by non-random chromosomal gains, involving combinations of trisomy 9, 12, 14, 15, and 17. With a median gain of three chromosomes, leukemia emerged after a prolonged latency from a preleukemic B cell precursor cell population displaying more diverse aneuploidy. Transition from preleukemia to overt disease in Eμ-Ret mice is associated with acquisition of heterogeneous genomic abnormalities affecting the expression of genes implicated in pediatric B-ALL. The development of abnormal centrosomes in parallel with aneuploidy renders both preleukemic and leukemic cells sensitive to inhibitors of centrosome clustering, enabling targeted in vivo depletion of leukemia-propagating cells. This study reveals the Eμ-Ret mouse to be a novel tool for investigating HD-ALL leukemogenesis, including supervision and selection of preleukemic aneuploid clones by the immune system and identification of vulnerabilities that could be targeted to prevent relapse.

2024-04-01 | GSE257537 | GEO

RNA-seq of Hyperdiploid Pediatric Acute Lymphoblastic Leukemia

Project description:RNA-seq of Hyperdiploid Pediatric Acute Lymphoblastic Leukemia

| PRJNA171805 | ENA

Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia

Project description:Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia

| PRJNA649423 | ENA

Germline genomic variations associated with childhood acute lymphoblastic leukemia

Project description:We identified germline single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL) and its subtypes. Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed (P<1x10-5) between a pediatric ALL population (n=317) and non-ALL controls (n=17,958). Six of these SNPs differed (P≤0.05) in allele frequency among four ALL subtypes. Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P=1.4x10-15, odds ratio[OR]=1.91; rs10994982, P=5.7x10-9, OR=1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P=1.62 x10-5, OR=2.17; rs10994982, P=0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n=124 children with ALL) (P=0.003 and P=0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline genomic variations affect susceptibility to and characteristics of specific ALL subtypes. We used microarrays to detail the global program of gene expression in primary leukemic blasts cells from children diagnosed with acute lymphoblastic leukemia.

2009-08-16 | E-GEOD-17195 | biostudies-arrayexpress

Immune stress suppresses innate immune signaling in preleukemic precursor B cells to cause leukemia

Project description:We used microarrays to investigate gene expression changes in leukemic bone marrow from Pax5+/-;Myd88+/- mice compared with bone marrow precursor B cells from WT mice and to study the effect of Myd88 downregulation in healthy Pax5+/- proB cells. The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children; germline or somatic alterations affecting transcription factor genes cause the appearance of preleukemic cells still compatible with normal hematopoiesis, and preclinical studies have shown that immune stressors can trigger the malignant transformation of these otherwise silent preleukemic precursors to full-blown B-ALL. Understanding how exposure to immune stressors drives this conversion is a longstanding and unsolved challenge. Here we unveiled a specific “gene/environmental factor” interaction triggering B-ALL development. Our data show that B-ALL development falls into the category of cancers associated with dysregulation of innate immunity, which plays a driving role in the clonal evolution of pre-malignant B-cell precursors toward B-ALL following exposure to an immune stress. Transcriptional profiling of B-ALL allowed the identification of an inflammation-dependent role for Myd88 as a key player in this process. A preleukemic B-cell-autonomous role was evidenced by a significant increase in B-ALL incidence upon Myd88 dowregulation in the leukemia-prone Pax5+/- model. Likewise, early innate immune response induction by Toll-like receptor (TLR) ligation during the preleukemic phase in Pax5+/- mice resulted in a significant delay of B-ALL development. These findings identify a central role for innate immunity dysregulation in B-ALL, with important implications for the understanding and potential therapeutic targeting of the preleukemic state in children.

2023-08-10 | GSE221597 | GEO

Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia [RNAseq_DAC_celllines]

Project description:Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia [RNAseq_DAC_celllines]

| PRJNA649432 | ENA

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