GEO series

Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation

GSE27816 Mus musculus Expression profiling by array 14 samples Submitted 2011/07/01 Platform GPL1261

Summary

Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation. These studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentitiation

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Also filed as BioProject PRJNA137933. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 21723200) ↗

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