The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues
and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia
CS Chen, JM Hilden, J Frestedt, PH Domer, R Moore, SJ Korsmeyer and JH Kersey
Department of Laboratory Medicine/Pathology, University of Minnesota,
Minneapolis 55455.
The chromosomal translocation, t(4;11)(q21;q23), is the most common type of
11q23 chromosomal abnormality, being highly prevalent in infant acute
leukemias and associated with a poor prognosis. The t(4;11) results in the
fusion of an 11q23 gene (MLL, HRX, Htrx-1, or ALL-1) and a 4q21 gene (AF-4
or FEL). To further evaluate the 4q21 gene and its role in t(4;11) acute
leukemia, we have cloned a 38-kb genomic region and mapped exons of the
AF-4 gene. The 4q21 breakpoints in 19 cases of t(4;11) acute leukemia were
analyzed by Southern analysis and pulsed- field gels. Seventeen of the 19
cases had breakpoints on chromosome 4q21 that were scattered in this 38 kb
region. Expression of the AF-4 gene was studied in a total of 28 various
nonhematopoietic, hematopoietic, and t(4;11) leukemic cell lines. The AF-4
gene was expressed in all cell lines as a major and a minor transcript. In
addition to the normal transcripts, two fusion transcripts from the
derivative 11 and derivative 4 chromosomes were identified in all t(4;11)
cell lines except B1, which had only the der(11) transcript. These findings
suggest that the breakpoints on 4q21 cluster over a broader area than do
the breakpoints in the 11q23 gene, and that der(11) encodes the fusion RNA
found consistently in leukemia cells.
Volume 82,
Issue 4,
pp. 1080-1085,
08/15/1993
Copyright © 1993 by The American Society of Hematology
