A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14).
The translocation t(10;14)(q24;q11) is an acquired change seen in 4% to 7% of T-cell acute lymphoblastic leukemias (T-ALL). We previously demonstrated that the translocation juxtaposes the T-cell receptor (TCR) delta-chain gene in chromosome 14q11 with a novel region in chromosome 10q24 and is likely catalyzed by recombinases normally involved in the generation of immunoglobulin and TCR diversity. We now present the sequence of a gene on chromosome 10 that lies immediately telomeric of the breakpoints in nine new ALL patients with acquired rearrangements in 10q24. The gene is a novel human homeobox gene and is expressed in leukemic cells from ALL patients with rearrangements in a defined chromosome 10 breakpoint cluster region, but not in other adult tissues or cell lines. This new gene has been designated HOX11. Our results strongly support a role for homeobox genes in oncogenesis and may represent the first example of a human cancer in which deregulated expression of an unaltered homeobox gene is involved in tumorigenesis.
University of Toronto Hospitals' Cancer Cytogenetics Program, Ontario, Canada.
I D
ID
Dubé
S
S
Kamel-Reid
C C
CC
Yuan
M
M
Lu
X
X
Wu
G
G
Corpus
S C
SC
Raimondi
W M
WM
Crist
A J
AJ
Carroll
J
J
Minowada
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D016415:Sequence Alignment; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C071250:TLX1 protein, human; D004247:DNA