Similar Datasets
Project description:The expression of the oncogene MYCN is upregulated in acute leukemia. However, the role of MYCN in leukemogenesis is poorly understood. We established multiple types of leukemia by retroviral overexpression of N-Myc in mice and studied the mechanism of leukemogenesis. Two types of hematopoietic stem cells and three types of hematopoietic progenitor cells highly purified from the bone marrow of adult C57BL/6 mice were transduced with N-Myc and transplanted into lethally irradiated mice. Acute leukemia developed from all these populations. Notably, not only B cell acute lymphoid leukemia, but also T cell acute lymphoid leukemia, acute myeloid leukemia, acute undifferentiated leukemia, and mixed phenotype acute leukemia developed, suggesting the multiple cells of origin, regardless types of leukemia. Moreover, leukemic stem cells were identified in Kit+Sca-1+Lin- bone marrow cells. RNA-seq data revealed the leukemia type-specific transcription profiles. Interestingly, acute undifferentiated leukemia appeared to be transcriptionally close to T cell acute lymphoid leukemia. Whole genome sequencing suggested that different types of leukemia arose associated with a large number of gene mutations induced by N-Myc overexpression but independent of retroviral integration sites. This study provides a new mouse model in which varying types of leukemia develop by only one oncogene.
2023-03-01 | GSE146331 | GEO
Project description:The expression of the oncogene MYCN is upregulated in acute leukemia. However, the role of MYCN in leukemogenesis is poorly understood. We established multiple types of leukemia by retroviral overexpression of N-Myc in mice and studied the mechanism of leukemogenesis. Two types of hematopoietic stem cells and three types of hematopoietic progenitor cells highly purified from the bone marrow of adult C57BL/6 mice were transduced with N-Myc and transplanted into lethally irradiated mice. Acute leukemia developed from all these populations. Notably, not only B cell acute lymphoid leukemia, but also T cell acute lymphoid leukemia, acute myeloid leukemia, acute undifferentiated leukemia, and mixed phenotype acute leukemia developed, suggesting the multiple cells of origin, regardless types of leukemia. Moreover, leukemic stem cells were identified in Kit+Sca-1+Lin- bone marrow cells. RNA-seq data revealed the leukemia type-specific transcription profiles. Interestingly, acute undifferentiated leukemia appeared to be transcriptionally close to T cell acute lymphoid leukemia. Whole genome sequencing suggested that different types of leukemia arose associated with a large number of gene mutations induced by N-Myc overexpression but independent of retroviral integration sites. This study provides a new mouse model in which varying types of leukemia develop by only one oncogene.
2023-03-01 | GSE146330 | GEO
Project description:N-Myc overexpression leads to multiple types of acute leukemia in mice
| PRJNA610169 | ENA
Project description:N-Myc overexpression leads to multiple types of acute leukemia in mice [WGS]
| PRJNA610170 | ENA
Project description:N-Myc overexpression leads to multiple types of acute leukemia in mice [RNA-Seq]
| PRJNA610171 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-02 | E-GEOD-52279 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-02-20 | GSE111922 | GEO
Project description:To assess the role of the CALM-AF10 fusion gene in leukemic transformation in vivo, we generated transgenic mice that expressed a CALM-AF10 fusion gene. Depending on the transgenic line, at least 40% to 50% of the F(1) generation mice developed acute leukemia at a median age of 12 months. Leukemic mice typically had enlarged spleens, invasion of parenchymal organs with malignant cells, and tumors with myeloid markers such as myeloperoxidase, Mac1, and Gr1. Although most leukemias were acute myeloid leukemia, many showed lymphoid features, such as CD3 staining, or clonal Tcrb or Igh gene rearrangements. Mice were clinically healthy for the first 9 months of life and had normal peripheral blood hemograms but showed impaired thymocyte differentiation, manifested by decreased CD4(+)/CD8(+) cells and increased immature CD4(-)/CD8(-) cells in the thymus. Hematopoietic tissues from both clinically healthy and leukemic CALM-AF10 mice showed up-regulation of Hoxa cluster genes, suggesting a potential mechanism for the impaired differentiation. The long latency period and incomplete penetrance suggest that additional genetic events are needed to complement the CALM-AF10 transgene and complete the process of leukemic transformation.
| S-EPMC1986634 | biostudies-literature
Project description:Antiapoptotic BCL2 family members have been implicated in the pathogenesis of acute myelogenous leukemia (AML), but the functional significance and relative importance of individual proteins (e.g., BCL2, BCL-XL, and myeloid cell leukemia 1 [MCL1]) remain poorly understood. Here, we examined the expression of BCL2, BCL-XL, and MCL1 in primary human hematopoietic subsets and leukemic blasts from AML patients and found that MCL1 transcripts were consistently expressed at high levels in all samples tested. Consistent with this, Mcl1 protein was also highly expressed in myeloid leukemic blasts in a mouse Myc-induced model of AML. We used this model to test the hypothesis that Mcl1 facilitates AML development by allowing myeloid progenitor cells to evade Myc-induced cell death. Indeed, activation of Myc for 7 days in vivo substantially increased myeloid lineage cell numbers, whereas hematopoietic stem, progenitor, and B-lineage cells were depleted. Furthermore, Mcl1 haploinsufficiency abrogated AML development. In addition, deletion of a single allele of Mcl1 from fully transformed AML cells substantially prolonged the survival of transplanted mice. Conversely, the rapid lethality of disease was restored by coexpression of Bcl2 and Myc in Mcl1-haploinsufficient cells. Together, these data demonstrate a critical and dose-dependent role for Mcl1 in AML pathogenesis in mice and suggest that MCL1 may be a promising therapeutic target in patients with de novo AML.
| S-EPMC2877934 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-02-27 | E-GEOD-55408 | biostudies-arrayexpress