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The t(5;17) variant of acute promyelocytic leukemia expresses a
nucleophosmin-retinoic acid receptor fusion
RL Redner, EA Rush, S Faas, WA Rudert and SJ Corey
Department of Medicine, University of Pittsburgh Medical Center, PA 15213,
USA.
We have studied an acute promyelocytic leukemia (APL) patient with a
variant t(5;17)(q32;q12). This translocation fuses the gene for the
nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor
alpha (RARA). Two alternatively spliced transcripts are expressed, which
differ in 129 bases immediately upstream of the RARA sequence. The NPM
sequences contained in the shorter NPM-RAR cDNA are identical to the NPM
sequences contained in the NPM-ALK fusion gene expressed in t(2;5)
lymphomas. The RARA sequences are the same as the RARA sequences found in
the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL,
respectively. Both NPM-RAR transcripts fuse NPM and RARA sequence in the
same reading frame, to generate translation products of 57 kD and 62 kD.
Both NPM-RAR proteins are expressed in the patient's leukemic cells, along
with wild-type RARA derived from the uninvolved allele. In transcriptional
assays using a retinoic acid response element reporter construct, both
NPM-RAR fusion proteins act as retinoic acid-dependent transcriptional
activators. This case defines a third class of APL rearrangements, all of
which generate fusion proteins of RARA.
Volume 87,
Issue 3,
pp. 882-886,
02/01/1996
Copyright © 1996 by The American Society of Hematology
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