BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia.
The molecular basis of human leukemia is heterogeneous. Cytogenetic findings are increasingly associated with molecular abnormalities, some of which are being understood at the functional level. Specific therapies can be developed based on such knowledge. To search for new genes in the acute leukemias, we performed a representational difference analysis. We describe a human gene in chromosome 8q22.3, BAALC (brain and acute leukemia, cytoplasmic), that is highly conserved among mammals but evidently absent from lower organisms. We characterized BAALC on the genomic level and investigated its expression pattern in human and mouse, as well as its complex splicing behavior. In vitro studies of the protein showing its subcellular localization suggest a function in the cytoskeleton network. Two isoforms are specifically expressed in neuroectoderm-derived tissues, but not in tumors or cancer cell lines of nonneural tissue origin. We show that blasts from a subset of patients with acute leukemia greatly overexpress eight different BAALC transcripts, resulting in five protein isoforms. Among patients with acute myeloid leukemia, those overexpressing BAALC show distinctly poor prognosis, pointing to a key role of the BAALC products in leukemia. Our data suggest that BAALC is a gene implicated in both neuroectodermal and hematopoietic cell functions.
Tanner
S M
SM
Human Cancer Genetics Program, Ohio State University, 646 Medical Research Facility, 420 West 12th Avenue, Columbus, OH 43210, USA.
Austin
J L
JL
Leone
G
G
Rush
L J
LJ
Plass
C
C
Heinonen
K
K
Mrózek
K
K
Sill
H
H
Knuutila
S
S
Kolitz
J E
JE
Archer
K J
KJ
Caligiuri
M A
MA
Bloomfield
C D
CD
de La Chapelle
A
A
D016475:3T3 Cells; D000208:Acute Disease; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
C442828:BAALC protein, human; C486703:Baalc protein, mouse; C486704:Baalc protein, rat; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D020033:Protein Isoforms