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The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in
t(4;11)(q21;q23)-containing acute lymphoblastic leukemia
JR Downing, DR Head, SC Raimondi, AJ Carroll, AM Curcio-Brint, TA Motroni, MG Hulshof, DJ Pullen and PH Domer
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN
38105.
The t(4;11)(q21;q23) is the most common translocation involving band 11q23
and is found predominantly in acute lymphoblastic leukemias (ALLs) of
infants. Recent studies have shown that this translocation involves the MLL
gene on chromosome 11 and the AF-4 gene on chromosome 4. Using
oligonucleotide primers derived from these genes, we established reverse
transcription-polymerase chain reaction (RT-PCR) assays for the detection
of the fusion transcripts from both the der(11) and der(4) chromosomes.
Using these assays we analyzed 23 pediatric cases of t(4;11) containing
ALL. RT-PCR analysis for the der(11)-derived MLL/AF-4 fusion transcript
resulted in its detection in every case at a sensitivity of greater than 1
leukemic cell in 10(5) cells. Sequence analysis of MLL/AF-4 PCR products
demonstrated fusion mRNAs resulting from breaks in MLL introns 6, 7, or 8,
with alternative splicing to one of three exons in the AF-4 gene. In
contrast, analysis for the der(4)-derived transcript resulted in the
detection of this chimeric mRNA in only 84% of the cases analyzed. These
data suggest that the critical chimeric gene product involved in the
establishment of the leukemic clone is derived from the der(11) chromosome.
Moreover, these data demonstrate the utility of the RT-PCR assay for the
der(11)- encoded message both for diagnosing t(4;11)-containing leukemia
and for monitoring patients for minimal residual disease.
Volume 83,
Issue 2,
pp. 330-335,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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