In vitro approaches have also demonstrated the potential of TLX1 to disrupt normal hematopoietic processes and promote the immortalization of murine progenitor cells derived from various hematopoietic sources, including bone marrow, fetal liver, yolk sac and embryonic stem cells (reviewed in). Several studies have provided evidence that TLX1 induces progenitor immortalization by blocking differentiation while concurrently increasing replicative capacity. It was reported that transduction of primary murine bone marrow progenitors with TLX1 retroviral vectors readily yields immortalized cell lines. These TLX1-immortalized cell lines display a strict dependence on interleukin 3 (IL-3; multicolony stimulating factor) for their survival and proliferation in culture, retain a diploid karyotype and are not leukemogenic when injected into sublethally irradiated syngeneic mice. The cell lines express surface antigens that are present on precursors of multiple hematopoietic lineages but their combined morphological and phenotypic properties are most compatible with immature cells belonging to the myeloid lineage. It was suggested that they might represent a bipotential monocytic-granulocytic precursor since they can be stimulated to partially differentiate along the monocyte/macrophage and granulocyte lineages (into CD11b/Mac-1+ Ly-6G/Gr-1+ cells) upon treatment with phorbol myristate acetate .
Robert G Hawley, The DN2 Myeloid-T (DN2mt) Progenitor is a Target Cell for Leukemic Transformation by the TLX1 Oncogene
Last date updated on December, 2024
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