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Detection of DNA rearrangements in the AML1 and ETO loci and of an AML1/ETO
fusion mRNA in patients with t(8;21) acute myeloid leukemia
G Nucifora, DJ Birn, P Erickson, J Gao, MM LeBeau, HA Drabkin and JD Rowley
Department of Medicine, University of Chicago, IL.
The (8;21)(q22;q22) translocation is a frequent karyotypic abnormality seen
in approximately 40% of patients with acute myeloid leukemia subtype M2
(AML-M2) and an abnormal karyotype. The translocation interrupts two genes,
AML1 on chromosome 21 and ETO on chromosome 8, that are consequently fused
in the der(8) chromosome to produce a novel chimeric gene and message.
Selected genomic DNA probes from chromosome 21 and from chromosome 8 near
the breakpoint junction detect rearrangements in the DNA of about 80% of
the patients with the rearrangement at diagnosis and in relapse. We
analyzed the DNA of 20 patients with t(8;21) AML by standard Southern blot
with probes originating from chromosomes 21 and 8 near the breakpoint
junction, and we identified rearranged bands in 17 of the 20 patients at
diagnosis and in relapse. We also used the polymerase chain reaction (PCR)
with appropriate primers from the AML1 and ETO genes to amplify the cDNAs
from a cell line with the t(8;21) and from seven AML patients with the
t(8;21). We detected a fused transcript in the cell line and in all of the
patients analyzed, including three patients who did not show any
rearrangement by Southern blot analysis and one patient in hematologic
remission, who later relapsed. Combining the results from Southern blot and
PCR analysis, we could detect the t(8;21) in all of the patients tested.
These results indicate that, whereas several DNA probes used as genetic
markers do detect the t(8;21) in most, but not all Southern blots of
patients with AML, PCR amplification with primers from AML1 and ETO can be
used as a more sensitive and accurate means for detecting this chromosomal
abnormality, and for observing the patients' response to therapy.
Volume 81,
Issue 4,
pp. 883-888,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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