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The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL) in cooperation with mutant TP53

ABSTRACT: The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL) in cooperation with mutant TP53

PROVIDER: PRJNA844994 | ENA |

REPOSITORIES: ENA

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The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL)

Project description:The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion in primary erythroblasts in fetal liver-derived erythroblasts from wild-type (C57/B6) mice. To better characterize alteration in chromatin accessibility due to NFIA-ETO2 expression, we analyzed accessible chromatin state by ATAC sequencing from cells kept in 24h in differentiation-inducing medium (DM)

2023-02-08 | GSE205392 | GEO

The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL) in cooperation with mutant TP53

Project description:The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion or an in active NFIA-ETOdeltaNHR4 mutant in primary erythroblasts in fetal liver-derived erythroblasts from either wild-type (C57/B6) or TP53R248Q (HUPKI) mice. Gene expression was determined by RNA sequencing from cells kept in maintenance medium (MM) or 24h in differentiation-inducing medium (DM)

2023-02-09 | GSE205420 | GEO

Effect of NFIA-ETO2 gene fusion on MEL cells during proliferation and impaired erythroid differentiation.

2023-02-09 | GSE205407 | GEO

Location of NFIA-ETO2 binding site on genome in MEL cells

Project description:The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion in MEL cells. To better identify direct target gene loci, we sequenced NFIA-ETO2-associated immunoprecipitated chromatin and histone modifications.

2023-02-09 | GSE205397 | GEO

The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL)

Project description:The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL)

| PRJNA844961 | ENA

The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53

Project description:The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53

| PRJNA845219 | ENA

The NFIA-ETO2 fusion blocks erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53.

Project description:The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation, so far, exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address the role for the pathogenesis of the disease, we facilitated the expression of the NFIA-ETO2 fusion in murine erythroblasts (EBs). We observed that NFIA-ETO2 significantly increased proliferation and impaired erythroid differentiation of murine erythroleukemia cells and of primary fetal liver-derived EBs. However, NFIA-ETO2-expressing EBs acquired neither aberrant in vitro clonogenic activity nor disease-inducing potential upon transplantation into irradiated syngenic mice. In contrast, in the presence of 1 of the most prevalent erythroleukemia-associated mutations, TP53R248Q, expression of NFIA-ETO2 resulted in aberrant clonogenic activity and induced a fully penetrant transplantable PEL-like disease in mice. Molecular studies support that NFIA-ETO2 interferes with erythroid differentiation by preferentially binding and repressing erythroid genes that contain NFI binding sites and/or are decorated by ETO2, resulting in a activity shift from GATA- to ETS-motif-containing target genes. In contrast, TP53R248Q does not affect erythroid differentiation but provides self-renewal and survival potential, mostly via downregulation of known TP53 targets. Collectively, our work indicates that NFIA-ETO2 initiates PEL by suppressing gene expression programs of terminal erythroid differentiation and cooperates with TP53 mutation to induce erythroleukemia.

| S-EPMC10646783 | biostudies-literature

Effect of NFIA-ETO2 gene fusion on MEL cells during proliferation and impaired erythroid differentiation.

Project description:Effect of NFIA-ETO2 gene fusion on MEL cells during proliferation and impaired erythroid differentiation.

| PRJNA844979 | ENA

The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-09 | GSE205437 | GEO

Location of NFIA-ETO2 binding site on genome in MEL cells

Project description:Location of NFIA-ETO2 binding site on genome in MEL cells

| PRJNA845216 | ENA