Gene expression study of leukemic and premalignant hematopoietic tissues from NUP98-PHF23 (NP23) mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54787 | GEO | 2014/03/06
SECONDARY ACCESSION(S): PRJNA237650
REPOSITORIES: GEO
Similar Datasets
Project description:NUP98-PHF23 is oncogenic and results in a Hoxa/b + Meis1 overexpression in NP23 leukemias and in premalignant (clinically healthy) hematopoietic tissues. Gene expression profiles from AML, pre-T LBL and B-ALL were compared to wild type bone marrow, thymus and spleen tissues respectively. Similarly, gene expression profiles from premalignant (clinically healthy) NP23 bone marrow, thymus and spleen were compared to wild type bone marrow, thymus and spleen tissues respectively. 106A and 748T lymphoblastic cell lines were compared to wild type thymic tissue.
2014-03-06 | E-GEOD-54787 | biostudies-arrayexpress
Project description:We analyzed the genome wide localization of H3K4me3, H3K27me3 and the NUP98-PHF23 (with V5 tag) fusion protein which binds H3K4me3 via its PHD finger, using ChIP-seq. Results correlated with gene expression profiles. NUP98-PHF23 bound only 1.6% of H3K4me3 marks including Hoxa/b + Meis1. Assess H3K4me3 and H3K27me3 histone marks, and correlate these marks with chromatin binding of the NP23 fusion protein using lymphoblast and myeloblast cell lines derived from NP23 leukemias.
2014-03-06 | E-GEOD-54786 | biostudies-arrayexpress
Project description:We analyzed the genome wide localization of H3K4me3, H3K27me3 and the NUP98-PHF23 (with V5 tag) fusion protein which binds H3K4me3 via its PHD finger, using ChIP-seq. Results correlated with gene expression profiles. NUP98-PHF23 bound only 1.6% of H3K4me3 marks including Hoxa/b + Meis1.
2014-03-06 | GSE54786 | GEO
Project description:The dysregulation of plant homeodomain (PHD) fingers has been implicated in several human diseases, including cancer. In a subset of aggressive acute myeloid leukemia (AML), chromosomal translocations that involve nucleoporin 98 (NUP98), a component of the nuclear pore complex, and a PHD finger-containing protein, such as KDM5A/JARID1A, PHF23 and BPTF, generate potent oncoproteins (namely NUP98-KDM5A, NUP98-PHF23 and NUP98-BPTF; or together termed as NUP98-PHD fusions) that are able to arrest hematopoietic differentiation and induce acute myeloid leukemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukemic transformation. An overlap of NUP98-KDM5A oncoprotein binding sites and H3K4me3-positive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq together with NMR analysis of the H3K4me3-binding sites of the PHD fingers from PHF23, KDM5A and BPTF suggests a common PHD finger-dependent mechanism that promotes leukemogenesis by this type of NUP98-PHD finger fusions. Disulfiram (DS), a small molecule compound that directly targets the PHD finger, shows anti-proliferation effects in AML cells expressing NUP98-PHD through the conserved inhibitory mechanism. Our findings highlight the direct correlation between the abilities of NUP98-PHD finger fusion chimeras to associate with H3K4me3-enriched chromatin and leukemic transformation.
2020-07-13 | GSE146693 | GEO
Project description:Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion
| PRJNA611626 | ENA
Project description:We report Illumina next generation RNA sequencing (RNAseq) of NUP98-HOXA9 in vitro transformed murine LSKs upon genetic deletion of Mll1. These gene expression data illustrate that Mll1 regulates Hoxa, Hoxb and Meis1 expression in NUP98-HOXA9 transformed murine BM cells.
2016-12-11 | GSE75997 | GEO
Project description:B-1 and B-2 lymphocytes are derived from distinct developmental pathways, and represent layered arms of the innate and adaptive immune systems, respectively. In contrast to the majority of murine B- cell malignancies, which stain positive with the B220 antibody, we discovered a novel form of B-cell leukemia in NUP98-PHF23 (NP23) transgenic mice. The immunophenotype (Lin- B220 - CD19+ AA4.1+) was identical to B-1 progenitor cells, and VH gene usage was skewed toward 3’ V regions, similar to murine fetal liver B-cells. We performed RNA sequencing and determined that the expression profile of these leukemias was most similar to fetal liver pro B fraction BC, a known source of B-1 B cells, further supporting a B-1 progenitor origin of these leukemias. The NP23 B-1 progenitor ALLs acquired spontaneous mutations in both Bcor and Jak pathway (Jak1/2/3 and Stat5a) genes, supporting a hypothesis that mutations in three critical pathways (stem cell self-renewal, B-cell differentiation, and cytokine signaling) collaborate to induce B-cell precursor (BCP) ALL. Finally, the Tslp cytokine is required for murine B- 1 development, and chromosomal rearrangements resulting in overexpression of the TSLP receptor (CRLF2) are present in some high risk BCP ALL patients (referred to as CRLF2r ALL). Gene expression profiles of NP23 pro-B1 ALL were more similar to CRLF2r ALL than non-CRLF2r ALL, and analysis of VH gene usage from CRLF2r ALL patients demonstrated preferential usage of VH regions used by human B-1 B-cells, leading to the suggestion that this subset of BCP ALL patients have a malignancy of B-1, rather than B-2 B-cell origin.
2018-10-10 | GSE104769 | GEO
Project description:RNA sequencing of murine Nup98-Phf23-driven pro-B1 ALL
| PRJNA413788 | ENA
Project description:Chromosomal NUP98-PHF23 translocation is associated with an aggressive form of acute myeloid leukemia (AML) and poor survival rate. Here, we report the molecular mechanisms by which NUP98-PHF23 recognizes the histone mark H3K4me3 and is inhibited by small molecule compounds, including disulfiram that directly targets the PHD finger of PHF23 (PHF23PHD). Our data support a critical role for the PHD fingers of NUP98-PHF23, and related NUP98-KDM5A and NUP98-BPTF fusions in driving leukemogenesis, and demonstrate that blocking this interaction in NUP98-PHF23 expressing AML cells leads to cell death through necrotic and late apoptosis pathways. An overlap of NUP98-KDM5A oncoprotein binding sites and H3K4me3-positive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq, together with NMR analysis of the H3K4me3-binding sites of the PHD fingers from PHF23, KDM5A and BPTF, suggests a common PHD finger-dependent mechanism that promotes leukemogenesis by this type of NUP98 fusions. Our findings highlight the direct correlation between the abilities of NUP98-PHD finger fusion chimeras to associate with H3K4me3-enriched chromatin and leukemic transformation.
| S-EPMC7335091 | biostudies-literature
Project description:Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.
2017-02-28 | GSE93923 | GEO