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ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear
protein with transcriptional activation potential in lymphoid and myeloid
cells
JE Rubnitz, J Morrissey, PA Savage and ML Cleary
Department of Pediatrics, Stanford University School of Medicine, CA
94305-5324.
Chromosome band 11q23 is the site of recurring translocations with a
variety of partner chromosomes in myeloid and lymphoid acute leukemias,
infant leukemias, and treatment-induced secondary acute myelogenous
leukemia. The translocation breakpoints cluster in a restricted region of
the HRX gene resulting in fusion genes that encode an N-terminal portion of
Hrx fused to various partner proteins. We have characterized the
transcriptional transactivation properties of Enl, a protein that is fused
to Hrx in t(11;19) leukemias. Enl is a nuclear protein that is capable of
activating transcription from synthetic reporter genes in both lymphoid and
myeloid cells, as well as in yeast. Deletion mutagenesis demonstrated that
the minimal portion of Enl required for activation of transcription was
localized to its C-terminal 90 amino acids. This region is highly conserved
between Enl and the t(9;11) fusion partner Af-9 and is retained in all
Hrx-Enl and Hrx-Af9 fusion proteins. Thus, the leukemogenic contribution
and transcriptional activation potential of Enl colocalize to its highly
conserved carboxy terminus, suggesting that Hrx-Enl chimeric proteins
mediate alterations in the transcription program of t(11;19)-bearing cells.
Volume 84,
Issue 6,
pp. 1747-1752,
09/15/1994
Copyright © 1994 by The American Society of Hematology
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