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Blood, 1 July 2002, Vol. 100, No. 1, pp. 89-95
HEMATOPOIESIS
A human Mix-like homeobox gene MIXL shows functional
similarity to Xenopus Mix.1
Wei Guo,
Agnes Pui-yee
Chan,
Hong Liang,
Eric D. Wieder,
Jeffrey J. Molldrem,
Laurence D. Etkin, and
Lalitha Nagarajan
From the Department of Molecular Genetics and the
Department of Blood and Marrow Transplantation, University of Texas
M. D. Anderson Cancer Center, Houston.
Molecular events involved in specification of early
hematopoietic system are not well known. In Xenopus, a
paired-box homeodomain family (Mix.1-4) has been implicated in this
process. Although Mix-like homeobox genes have been isolated from
chicken (CMIX) and mice
(Mml/MIXL1), isolation of a human Mix-like gene
has remained elusive. We have recently isolated and characterized a
novel human Mix-like homeobox gene with a predicted open reading frame
of 232 amino acids designated the Mix.1 homeobox (Xenopus
laevis)-like gene (MIXL). The overall identity of
this novel protein to CMIX and Mml/MIXL1 is 41% and 69%,
respectively. However, the identity in the homeodomain is 66% to that
of Xenopus Mix.1, 79% to that of CMIX, and 94% to
that of Mml/MIXL1. In normal hematopoiesis, MIXL expression
appears to be restricted to immature B- and T-lymphoid cells.
Several acute leukemic cell lines of B, T, and myeloid lineage express
MIXL suggesting a survival/block in differentiation advantage.
Furthermore, Xenopus animal cap assay revealed that MIXL
could induce expression of the  -globin gene, suggesting a
functional conservation of the homeodomain. Isolation of the MIXL gene is the first step toward understanding novel
regulatory circuits in early hematopoietic differentiation and
malignant transformation.
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