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  • Title: The mechanism of hematopoietic progenitor cell immortalization by MLL-ENL.
    Author: Horton SJ, Williams O.
    Journal: Cell Cycle; 2006 Feb; 5(4):360-2. PubMed ID: 16479159.
    Abstract:
    The t(11;19) translocation gives rise to the MLL-ENL fusion protein and is frequently found in infant myeloid and lymphoid leukemias. Immortalized myeloid cell lines can be generated by expression of MLL-ENL in murine hematopoietic progenitors. By establishing myeloid cell lines with conditional expression of MLL-ENL, we recently demonstrated that MLL-ENL is necessary to maintain immortalization and sustain the expression of a characteristic pattern of Hox genes. The cell lines can be induced to undergo terminal differentiation by inhibition of MLL-ENL expression or by treatment with G-CSF. Expression of Hoxa genes is reduced in cells differentiating as a result of MLL-ENL loss, but is maintained in G-CSF treated cells. Thus, although aberrant maintenance of Hoxa gene expression may play an important role in MLL-ENL induced leukemia, the contribution of this pathway to immortalization is critically dependent on the cytokine environment of the immortalized myeloid cells.
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