Role of Tet2 inactivation in mouse hematopoiesis
type: Dataset
description: Acquired loss-of-function mutations of TET2 gene are frequently observed in patients with myeloid malignancies, including acute myeloblastic leukemia, myeloproliferative neoplasm, myelodysplastic syndrome, and chronic myelomonocytic leukemia (CMML). The Ten-Eleven-Translocation (TET) family proteins are 2-oxoglutarate/Fe(II)-dependent dioxygenases that catalyze the conversion of 5-methyl-cytosine into 5-hydroxymethyl-cytosine, which is proposed to constitute a first step toward cytosine demethylation. To study the function of Tet2 in murine hematopoiesis, we developed two mouse models in which the catalytic domain of the protein is disrupted. In both models, Tet2 deficiency leads to the progressive expansion of the immature hematopoietic compartment that includes stem cell and multipotent progenitors. In addition, both Tet2-deficient animals display abnormalities of erythroid, megakaryocytic, myelo-monocytic and lymphoid lineages, recapitulated in competitive transplantation assays. With age, Tet2-deficient mice develop bona fide myeloid tumors. All these properties were shown to be cell-autonomous by bone marrow cells transplantation and in vitro assays. Together these data suggest that TET2 activity is essential for normal homeostasis of the hematopoietic system. Its inactivation results in the development of hematologic disorders resembling human CMML myeloid disorders. TET2 deficiency endows the cells with a competitive advantage over wild type cells, induces hematopoietic differentiation abnormalities but is not responsible for full cellular transformation. The latency observed for CMML development in mouse models of Tet2 deficiency suggests a requirement for cooperating mutations, such other epigenetic regulator alterations.
identifier: NNT: 2012PA11T038
issued: 2026-05-05T10:12:03.335643
language: fr
modified: 2026-05-05T10:12:03.335647
contact point: Organization
  fn: CCSD
keyword: cmml
keyword: hemopathies-malignes
keyword: infoeu-reposemanticsdoctoralthesis
keyword: lmmc
keyword: malignancies
keyword: modelisation
keyword: mouse-models
keyword: sdvgenlife-sciences-q-biogenetics
keyword: suppresseur-de-tumeur
keyword: tet2
keyword: theses
keyword: tumor-suppressor-gene
landing page: https://theses.hal.science/tel-00996633

Role of Tet2 inactivation in mouse hematopoiesis
type: Distribution
format: HTML
issued: 2026-05-05T10:12:03.342755
modified: 2026-05-05T10:12:03.316591
access URL: https://theses.hal.science/tel-00996633

test_moissonnage_selune
type: Agent