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ChIP sequencing of ETV6-NCOA2 H3K27Ac profile in T/M mixed-phenotype acute leukemia

ABSTRACT: H3K27Ac ChIP-sequencing of CD34 positive cord blood cells expressing either ETV6-NCOA2 or empty-vector in-vitro and ETV6-NCOA2 patient derived xenograft.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161624 | GEO | 2022/05/16

REPOSITORIES: GEO

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ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6-NCOA2 human]

Project description:Exparession profiling of ETV6-NCOA2 at different stages of disease dEmpty vectorelopment: CD34 cord blood cells transduced with ETV6-NCOA2-GFP or with empty vector-GFP, CD34 cord blood cells transduced with ETV6-NCOA2-NGFR or ETV6-NCOA2-NGFR + NOTCH1-L1601PdP-GFP and transplanted in NSGS mice, and ETV6-NCOA2 patient derived xenografts.

2022-05-16 | GSE161702 | GEO

ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6_NCOA2_Mouse_in_vitro]

Project description:Exparession profiling of lineage negative bone marrow cells from C57B/6 mice expressing either ETV6-NCOA2, KAT6-NCOA2 or empty-vector after five days in in-vitro culture.

2022-05-16 | GSE161703 | GEO

ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6-NCOA2 human]

Project description:ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6-NCOA2 human]

| PRJNA679212 | ENA

RNA sequencing of ETV6-NCOA2 expression in CD34 positive cord blood cells

2022-05-16 | GSE162230 | GEO

ETV6-NCOA2 expression in CD34 positive cord blood cells

Project description:ETV6-NCOA2 expression in CD34 positive cord blood cells

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ChIP sequencing of ETV6-NCOA2 H3K27Ac profile in T/M mixed-phenotype acute leukemia

Project description:ChIP sequencing of ETV6-NCOA2 H3K27Ac profile in T/M mixed-phenotype acute leukemia

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ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6_NCOA2_Mouse_in_vitro]

Project description:ETV6-NCOA2 expression profile in T/M mixed-phenotype acute leukemia [ETV6_NCOA2_Mouse_in_vitro]

| PRJNA679211 | ENA

RNA sequencing of ETV6-NCOA2 expression in CD34 positive cord blood cells

Project description:RNA sequencing of ETV6-NCOA2 expression in CD34 positive cord blood cells

| PRJNA681160 | ENA

ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells.

Project description:Mixed-phenotype acute leukemia is a rare subtype of leukemia in which both myeloid and lymphoid markers are co-expressed on the same malignant cells. The pathogenesis is largely unknown, and the treatment is challenging. We previously reported the specific association of the recurrent t(8;12)(q13;p13) chromosomal translocation that creates the ETV6-NCOA2 fusion with T/myeloid leukemias. Here we report that ETV6-NCOA2 initiates T/myeloid leukemia in preclinical models; ectopic expression of ETV6-NCOA2 in mouse bone marrow hematopoietic progenitors induced T/myeloid lymphoma accompanied by spontaneous Notch1-activating mutations. Similarly, cotransduction of human cord blood CD34+ progenitors with ETV6-NCOA2 and a nontransforming NOTCH1 mutant induced T/myeloid leukemia in immunodeficient mice; the immunophenotype and gene expression pattern were similar to those of patient-derived ETV6-NCOA2 leukemias. Mechanistically, we show that ETV6-NCOA2 forms a transcriptional complex with ETV6 and the histone acetyltransferase p300, leading to derepression of ETV6 target genes. The expression of ETV6-NCOA2 in human and mouse nonthymic hematopoietic progenitor cells induces transcriptional dysregulation, which activates a lymphoid program while failing to repress the expression of myeloid genes such as CSF1 and MEF2C. The ETV6-NCOA2 induced arrest at an early immature T-cell developmental stage. The additional acquisition of activating NOTCH1 mutations transforms the early immature ETV6-NCOA2 cells into T/myeloid leukemias. Here, we describe the first preclinical model to depict the initiation of T/myeloid leukemia by a specific somatic genetic aberration.

| S-EPMC9906988 | biostudies-literature

Identification of ETV6 bound protein by affinity purification of ETV6-HA fusion protein in REH cells

Project description:To determine the protein partners of ETV6, we expressed ETV6 and HA-tagged ETV6 in Reh pre-B leukemic cells. Anti-HA magnetic beads were used for affinity purification of ETV6-HA (and ETV6 control) from the nuclear and cytoplasmic fraction. Following purification on-beads digest and LC-MS/MS experiments were performed at the Proteomics platform of the CHU de Quebec Research Center, Quebec, Canada.

2022-01-26 | PXD031001 | Pride

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