Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA95819 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profiling of three cell populations of a CALM/AF10 leukemia mouse model Keywords: expression profiling
2006-07-20 | GSE5030 | GEO
Project description:The translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.
2017-06-19 | GSE58853 | GEO
Project description:The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion.
2011-10-05 | GSE27512 | GEO
Project description:CALM (Clathrin Assembly Lymphoid Myeloid Leukemia)-AF10, a fusion gene frequently observed in acute myeloid leukemia (AML), is caused by the t(10;11)(q13;q14) translocation, and is associated with poor prognosis. In this study, we demonstrate that the CCCTC-binding factor (CTCF) is crucial for both the initiation and maintenance of CALM-AF10-induced AML (CALM-AF10 AML). To investigate the role of CTCF in CALM-AF10 AML, we used hematopoietic stem and progenitor cells (HSPCs) from conditional knockout (KO) mice and immortalized them by introducing the CALM-AF10 fusion gene to generate CALM-AF10 AML models. Our in vivo experiments revealed that CTCF deficiency significantly prolonged the survival of CALM-AF10 AML mice. Similarly, in vitro analyses showed that CTCF KO inhibited the colony-forming ability of CALM-AF10 AML cells and induced differentiation into macrophage-like cells. RNA sequencing (RNA-seq) of CTCF KO cells identified that the most downregulated gene was Transglutaminase 2 (TGM2). Chromatin immunoprecipitation followed by sequencing (ChIP-seq) showed that increase in levels of trimethylation of histone H3K27 as well as decrease in levels of trimethylation of histone H3K4 and acetylation of histone H3K27 were observed at the transcription start site (TSS) of the Tgm2 gene after CTCF KO. Knocking down (KD) TGM2 using small hairpin RNA (shRNA) in both CALM-AF10 AML cells and the human leukemic cell line U937, which expresses the CALM-AF10 fusion gene, resulted in reduced colony-forming ability and cell proliferation, alongside differentiation into macrophage-like cells. These results mirrored those observed with CTCF KO. Furthermore, treatment with GK921, a TGM2 inhibitor, yielded similar effects. Taken together, our findings suggest that CTCF regulates the expression of TGM2 by altering histone modifications at its TSS, thereby contributing to the maintenance of the undifferentiated state in CALM-AF10 AML. Given the efficacy of TGM2 inhibitors, such as GK921, against CALM-AF10 AML, TGM2 represents a promising therapeutic target for this leukemia subtype.
2025-12-03 | GSE281043 | GEO
Project description:The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion.
2011-10-05 | GSE27513 | GEO
Project description:CALM (Clathrin Assembly Lymphoid Myeloid Leukemia)-AF10, a fusion gene frequently observed in acute myeloid leukemia (AML), is caused by the t(10;11)(q13;q14) translocation, and is associated with poor prognosis. In this study, we demonstrate that the CCCTC-binding factor (CTCF) is crucial for both the initiation and maintenance of CALM-AF10-induced AML (CALM-AF10 AML). To investigate the role of CTCF in CALM-AF10 AML, we used hematopoietic stem and progenitor cells (HSPCs) from conditional knockout (KO) mice and immortalized them by introducing the CALM-AF10 fusion gene to generate CALM-AF10 AML models. Our in vivo experiments revealed that CTCF deficiency significantly prolonged the survival of CALM-AF10 AML mice. Similarly, in vitro analyses showed that CTCF KO inhibited the colony-forming ability of CALM-AF10 AML cells and induced differentiation into macrophage-like cells. RNA sequencing (RNA-seq) of CTCF KO cells identified that the most downregulated gene was Transglutaminase 2 (TGM2). Chromatin immunoprecipitation followed by sequencing (ChIP-seq) showed that increase in levels of trimethylation of histone H3K27 as well as decrease in levels of trimethylation of histone H3K4 and acetylation of histone H3K27 were observed at the transcription start site (TSS) of the Tgm2 gene after CTCF KO. Knocking down (KD) TGM2 using small hairpin RNA (shRNA) in both CALM-AF10 AML cells and the human leukemic cell line U937, which expresses the CALM-AF10 fusion gene, resulted in reduced colony-forming ability and cell proliferation, alongside differentiation into macrophage-like cells. These results mirrored those observed with CTCF KO. Furthermore, treatment with GK921, a TGM2 inhibitor, yielded similar effects. Taken together, our findings suggest that CTCF regulates the expression of TGM2 by altering histone modifications at its TSS, thereby contributing to the maintenance of the undifferentiated state in CALM-AF10 AML. Given the efficacy of TGM2 inhibitors, such as GK921, against CALM-AF10 AML, TGM2 represents a promising therapeutic target for this leukemia subtype.
2025-12-03 | GSE281045 | GEO
Project description:CALM (Clathrin Assembly Lymphoid Myeloid Leukemia)-AF10, a fusion gene frequently observed in acute myeloid leukemia (AML), is caused by the t(10;11)(q13;q14) translocation, and is associated with poor prognosis. In this study, we demonstrate that the CCCTC-binding factor (CTCF) is crucial for both the initiation and maintenance of CALM-AF10-induced AML (CALM-AF10 AML). To investigate the role of CTCF in CALM-AF10 AML, we used hematopoietic stem and progenitor cells (HSPCs) from conditional knockout (KO) mice and immortalized them by introducing the CALM-AF10 fusion gene to generate CALM-AF10 AML models. Our in vivo experiments revealed that CTCF deficiency significantly prolonged the survival of CALM-AF10 AML mice. Similarly, in vitro analyses showed that CTCF KO inhibited the colony-forming ability of CALM-AF10 AML cells and induced differentiation into macrophage-like cells. RNA sequencing (RNA-seq) of CTCF KO cells identified that the most downregulated gene was Transglutaminase 2 (TGM2). Chromatin immunoprecipitation followed by sequencing (ChIP-seq) showed that increase in levels of trimethylation of histone H3K27 as well as decrease in levels of trimethylation of histone H3K4 and acetylation of histone H3K27 were observed at the transcription start site (TSS) of the Tgm2 gene after CTCF KO. Knocking down (KD) TGM2 using small hairpin RNA (shRNA) in both CALM-AF10 AML cells and the human leukemic cell line U937, which expresses the CALM-AF10 fusion gene, resulted in reduced colony-forming ability and cell proliferation, alongside differentiation into macrophage-like cells. These results mirrored those observed with CTCF KO. Furthermore, treatment with GK921, a TGM2 inhibitor, yielded similar effects. Taken together, our findings suggest that CTCF regulates the expression of TGM2 by altering histone modifications at its TSS, thereby contributing to the maintenance of the undifferentiated state in CALM-AF10 AML. Given the efficacy of TGM2 inhibitors, such as GK921, against CALM-AF10 AML, TGM2 represents a promising therapeutic target for this leukemia subtype.
2025-12-03 | GSE281044 | GEO
Project description:Purpose: The goals of this study are to compare transcriptomes after shutting off the CALM-AF10, MLL-AF10 and MLL-AF9 fusion proteins in mouse AML cells. Furthermore, we also perform transcriptomic experiments to assess the changes in transcripts upon JAK1 deletion in mouse CALM-AF10 AML. Methods: Mouse AMLs cells grown in Mouse leukemia medium (see below) were treated with DMSO (Tet-On) or 4ug/ul Doxycycline (Tet-Off) and RNA was isolated to perform RNA-seq. RNA for CALM-AF10, MLL-AF10 was poly-A selected and MLL-AF9, total RNA was used to make RNAseq libraries using the NEB RNAseq lbrary prep kit. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the mouse genome (build mm9) and 60 million reads for MLL-AF9 data. Data analysis with BWA and TopHat workflows revealed genes that are significantly changed after shutting off the fusions or after deleting Jak1 in CALM-AF10 Jak1 floxed cells using the Cre recombinase. Conclusions:
2021-01-05 | GSE164181 | GEO
Project description:The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion. Global micro-RNA expression of bone marrow cells transduced with various constructs were compared. We used the empty vector, MIG, as a control and baseline. Four samples are tested with three biological replicates each.
2011-10-04 | E-GEOD-27512 | biostudies-arrayexpress
Project description:The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion. Global gene expression of bone marrow cells transduced with various constructs were compared. We used the empty vector, MIG, as a control and baseline. Four samples are tested with three biological replicates each.
2011-10-04 | E-GEOD-27513 | biostudies-arrayexpress