Date: 14 October 2005 HOX genes and leukaemia link

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Date 14 October 2005 HOX genes and leukaemia
link Cancer Research paper, Horton et al., to be
published on October 15th, 2005.  Not for use
before that date. The HOX family of genes were
first discovered to have a central role in embryo
development, where they help the organism define
which end is the head.  However, these genes also
play a role in blood cell development.  In new
work, researchers at the UCL Institute of Child
Health have investigated the links between a
particular chromosomal translocation involving
chromosomes 11 and 19 and aberrant HOX gene
expression.  This chromosomal translocation leads
to the production of the MLL-ENL fusion protein
which is found in many cases of infant leukaemia
and is associated with a poor outcome. MLL-ENL
immortalizes blood stem cells, this is the first
step in leukaemia.  Using a system in which the
presence of the MLL-ENL protein can be switched
off and on, the scientists have shown that
switching off MLL-ENL results in death of the
cells.  The work also shows that that the
presence of MLL-ENL leads to a unique pattern of
HOX gene expression which may be central to
turning normal blood stem cells into leukaemic
cells.  The potential clinical significance of
this is that therapies need to be developed which
combat the action of MLL-ENL by targetting
multiple HOX genes rather than one or two HOX
genes as previously thought said lead
researchers Dr Hugh Brady and Dr Owen Williams.
Rather than seeking a magic bullet aimed at a
single protein, we are looking for a quiver of
magic arrows, attacking multiple targets at
once.  The work was funded by the Children with
Leukaemia and the Leukaemia Research Fund.