Duplicated regions of AF-4 intron 4 at t(4;11) translocation breakpoints.
BACKGROUND
AF-4 is a common partner gene of MLL. AF-4 breakpoints occur in introns, but most AF-4 introns are uncharacterized.


RESULTS
We cloned AF-4 intron 4 and examined the frequency of breakpoints in this intron. The 5.8-kb intron is rich in repeat sequences and was the site of translocation in 3 of 17 leukemias with t(4;11). We cloned the der (11) and der (4) breakpoints and isolated the fusion transcripts in the cell line MV4-11 and in a de novo acute lymphoblastic leukemia (ALL). Both translocations joined MLL intron 6 and AF-4 intron 4. In MV4-11, 249 bases from AF-4 were present in both derivative chromosomes, indicating duplication. In the de novo ALL, duplication of 446 bases from MLL and AF-4 occurred. Reciprocal fusion transcripts were expressed.


CONCLUSIONS
Intronic sequence of AF-4 is useful for molecular diagnosis of t(4;11). Duplicated intronic regions suggest staggered chromosomal breakage.
Felix
C A
CA
Division of Oncology, The Children's Hospital of Philadelphia, Pennsylvania 19104-4318, USA. felix@email.chop.edu
Hosler
M R
MR
Slater
D J
DJ
Megonigal
M D
MD
Lovett
B D
BD
Williams
T M
TM
Nowell
P C
PC
Spinner
N B
NB
Owens
N L
NL
Hoxie
J
J
Croce
C M
CM
Lange
B J
BJ
Rappaport
E F
EF
D000293:Adolescent; D000328:Adult; D000368:Aged; D020087:Alu Elements; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured