Influence of DNA Methylation and Core Binding Factors in Expression of Leukemia Virus in Hemapoietic Stem Cells.
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Date
2011-10
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Abstract
Retroviral vectors based upon the Moloney murine leukemia virus (MLV) have been
used due to their high efficiency of stable gene transfer. Core binding factors (CBF) are
heterodimeric transcription factors containing a DNA binding Runx 1, Runx 2, or Runx 3
subunit, along with a non DNA binding CBF ẞ subunit. All four subunits are required at
one or more stages of hematopoiesis. This review describes the role of Runx1 and CBF ẞ
in the initiation of hematopoiesis in the embryo, and in the emergence of
hematopoietic stem cells. The core site in the Moloney murine leukemia virus (Moloney
MLV) enhancer was previously shown to be an important determinant of the T-cell
disease specificity of the virus. Mutation of the core site resulted in a significant shift in
disease specificity of the Moloney virus from T-cell leukemia to erythro-leukemia. It has
been shown that a protein that binds the core site, one of the core-binding factors is
highly expressed in thymus and is essential for hematopoiesis in stem cells. Earlier
studies suggest that CBF plays a critical role in mediating pathogenesis of Moloney MLV
in vivo. Spontaneous leukemia was not observed either upon CBF expression,
consistent with a model in which the increase in HSC and progenitor populations
represents a pre-leukemic state, and additional mutations are required for progression
to leukemia.
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Keywords
Leukemia, core binding factor, stem cell, methylation, hematopoiesis
Citation
Tyagi Manoj G, Kumar Aniket. Influence of DNA Methylation and Core Binding Factors in Expression of Leukemia Virus in Hemapoietic Stem Cells. British Journal of Medicine and Medical Research. 2011 Oct; 1(4): 223-228.