ALL-1 partial duplication in acute leukemia.
The ALL-1 gene, located on chromosome band 11q23, is fused to a variety of other genes by reciprocal chromosomal translocations present in 5-10% of human acute leukemias. We have recently reported the detection by Southern blot of ALL-1 gene rearrangements in adult patients with acute myeloid leukemia lacking cytogenetic evidence of 11q23 translocations. These include 2 of 19 patients with normal karyotypes as well as 3 of 4 patients with trisomy 11. To characterize the abnormal ALL-1 genes, we cloned the ALL-1 rearrangements from two patients with trisomy 11. Characterization of the clones, together with Southern blot analysis, indicates that the ALL-1 rearrangement in both patients is the result of a direct tandem duplication of a portion of the ALL-1 gene spanning exons 2-6. The partial ALL-1 duplication is also detected by Southern blot analysis in a patient with a normal karyotype. RNA PCR and DNA sequence analysis show that the partially duplicated ALL-1 gene is transcribed into mRNA capable of encoding a partially duplicated protein. Partial duplication of ALL-1, in which a portion of a putative protooncogene is fused with itself, represents an additional genetic mechanism for leukemogenesis. Our findings suggest that the presence of trisomy in malignancy may sometimes indicate the partial duplication of a cellular protooncogene.
Jefferson Cancer Institute, Jefferson Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107.
S A
SA
Schichman
M A
MA
Caligiuri
Y
Y
Gu
M P
MP
Strout
E
E
Canaani
C D
CD
Bloomfield
C M
CM
Croce
D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D015321:Gene Rearrangement; D006801:Humans; D007438:Introns; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014314:Trisomy
D017931:DNA Primers