N-Myc overexpression leads to multiple types of acute leukemia in mice [WGS]
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ABSTRACT: 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.
ORGANISM(S): Mus musculus
PROVIDER: GSE146331 | GEO | 2023/03/01
REPOSITORIES: GEO
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