Project description:Whole exome sequencing (the SureSelectXT Mouse All Exon Kit) was done on leukemias from NP23-NHD13 double transgenic mice with strain background designated “C57Bl6-NIH”.
2020-09-10 | GSE137542 | GEO
Project description:Whole exome sequencing of leukemias from NP23-NHD13 double transgenic mice
Project description:Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are frequently observed in a wide variety of hematologic malignancies, including myeloid and T-cell leukemias. In this study, we generated Idh2R140Q transgenic mice to examine the role of the Idh2R140Q mutation in leukemia. No leukemia developed in Idh2R140Q transgenic mice, suggesting a need for additional genetic events for leukemia development. Since myeloid cells from NUP98-HOXD13 fusion (NHD13) transgenic mice frequently acquire somatic Idh mutations when they transform to AML, we generated Idh2R140Q/NHD13 double transgenic mice. Idh2R140Q/NHD13 transgenic mice developed an immature T cell leukemia with an immunophenotype similar to double-negative 1 (DN1) or DN2 thymocytes. Idh2R140Q/NHD13 leukemic cells were enriched for an early thymic precursor transcriptional signature, and the gene expression profile for Idh2R140Q/NHD13 DN1/DN2 T-ALL closely matched that of human early/immature T cell precursor (EITP) ALL. Moreover, recurrent mutations found in EITP ALL patients, including KRAS, PTPN11, JAK3, SH2B3, and EZH2 were also found in Idh2R140Q/NHD13 DN1/DN2 T-ALL. In vitro treatment of Idh2R140Q/NHD13 thymocytes with enasidenib, a selective inhibitor of mutant IDH2, led to a marked decrease in leukemic cell proliferation. These findings demonstrate that Idh2R140Q/NHD13 mice can serve as a useful in vivo model for the study of EITP ALL development and therapy. We used gene expression arrays to compare the global gene expression profiles between Idh2R140Q/NHD13 DN1/DN2 T-ALL, non-DN1/DN2 cortical T-ALL (CD4+CD8+) and wild-type thymus.
Project description:We examined the patterns of gene expression of mouse thymic leukemias extracted from Mb1-CreDPB mice by RNA sequencing (RNA-seq). Our goal was to integrate RNA-seq data with whole-exome sequencing (WES) to determined secondary driver mutations of leukemogenesis in the absence of Spi-B and PU.1,
Project description:NUP98-PHF23 is oncogenic and results in a Hoxa/b + Meis1 overexpression in NP23 leukemias and in premalignant (clinically healthy) hematopoietic tissues.
Project description:Transcriptional profiling of young leaves of rice (Oryza sativa) comparing a control transgenic line transformed with p*7GWIWG2(I)-hpt with a double knockdown transgenic line of OsMOM1 genes. Rice has two orthologues (OsMOM1a and OsMOM1b) of Arabidopsis MOM1 gene, which transduces RNA-directed DNA methylation signals to repressive histone modification. To obtain the double knockdown line, at first, single knockdown lines for each OsMOM1 gene were produced with transformation using p*7GWIWG2(I)-hpt-OsMOM1a or p*7GWIWG2(I)-hpt-OsMOM1b. Then a double knockdown plant was selected from progenies of a sexual cross between the single knockdown lines. Both OsMOM1 constructs produce hairpin RNAs and efficiently silence the both target OsMOM1 genes. In the double knockdown line, neither of transcripts from OsMOM1 genes was detected with RNA blot. The double knockdown line might make levels of epigenetic marks (DNA and histone modifications) modified. Goal was to determine the effects of epigenetic change by knockdown of OsMOM1 genes on global gene expression in rice genome.
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.
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.
Project description:Blood samples from patients with myeloid malignancies were analyzed using whole exome sequencing (WES). Data set from genotyping by microarray of the same samples has been deposited in ArrayExpress under accession number E-MTAB-1845 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1845/).