Sm. Tanner et al., BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia, P NAS US, 98(24), 2001, pp. 13901-13906
Citations number
15
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The molecular basis of human leukemia is heterogeneous. Cytogenetic finding
s are increasingly associated with molecular abnormalities, some of which a
re being understood at the functional level. Specific therapies can be deve
loped based on such knowledge. To search for new genes in the acute leukemi
as, we performed a representational difference analysis. We describe a huma
n gene in chromosome 8q22.3, BAALC (brain and acute leukemia, cytoplasmic),
that is highly conserved among mammals but evidently absent from lower org
anisms. We characterized BAALC on the genomic level and investigated its ex
pression pattern in human and mouse, as well as its complex splicing behavi
or. In vitro studies of the protein showing its subcellular localization su
ggest a function in the cytoskeleton network. Two isoforms are specifically
expressed in neuroectoderm-derived tissues, but not in tumors or cancer ce
ll lines of nonneural tissue origin. We show that blasts from a subset of p
atients with acute leukemia greatly overexpress eight different BAALC trans
cripts, resulting in five protein isoforms. Among patients with acute myelo
id leukemia, those overexpressing BAALC show distinctly poor prognosis, poi
nting to a key role of the BAALC products in leukemia. Our data suggest tha
t BAALC is a gene implicated in both neuroectodermal and hematopoietic cell
functions.