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Gene regulation changes driven by wild type and cancer-associated mutant variants of Myc as B-cells convert to Lymphoma-like cells

ABSTRACT: cMyc plays a major role in lymphoma development. In addition, missense mutations including T58A and T58I the substitution mutations augment cMyc activity during lymphoma development. In this study, we characterized lymphoma-associated gene expression changes as increasing levels of wild type or mutant cMyc proteins progressively drive conversion of B-cells to lymphoma-like cells. To this end we established a cell system in which primary mouse B-cells were transduced with constructs that over-express the anti-apoptotic proteins, BMI1 and BCLXL and allow variable expression of cMyc (wild type, T58A or T58I) from a doxycycline-regulated promoter. Increased cMyc expression is associated with cell cycle entry, increased cell size and increased cell proliferation. Generally, gene programs required for cell growth and proliferation are induced while specific functions associated with B-cells are repressed. Mutant cMyc proteins cause differential effects, relative to each other and to wild type cMyc, that are focused on particular aspects of the cMyc-induced program.

ORGANISM(S): Mus musculus

PROVIDER: GSE122602 | GEO | 2021/11/15

REPOSITORIES: GEO

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