Two types of genomic rearrangements create alternative E2A-HLF fusion
proteins in t(17;19)-ALL
SP Hunger, PE Devaraj, L Foroni, LM Secker-Walker and ML Cleary
Department of Pathology, Stanford University School of Medicine, CA 94305.
The t(17;19)(q21-q22;p13.3) in acute lymphoblastic leukemia results in
creation of an E2A-HLF fusion protein with structural and functional
properties of a chimeric transcription factor. Two types of genomic
rearrangements underlie fusion of E2A with HLF. In type I rearrangements,
an insertion that codes for a portion of the chimera not found in either
wild type protein occurs between E2A exon 13- and HLF exon 4-encoded
sequences. This insertion is derived from a cryptic exon created at the
junction between chromosomes 17 and 19, and includes intronic portions of
both E2A and HLF with intervening nontemplated N nucleotides. Type II
rearrangements arise from more 5' breakpoints in E2A and result in fusion
cDNAs with E2A exon 12 spliced directly to HLF exon 4. Analysis of the
genomic structure of HLF shows that these different modes of protein fusion
result from selective constraints to maintain the proper HLF reading frame,
because a direct E2A exon 13 to HLF exon 4 splice would lead to translation
of a truncated E2A protein lacking any contribution from HLF. These
features underscore the requirement for DNA binding and/or dimerization
conferred by the bZIP portion of the E2A-HLF chimera in t(17;19)-ALL.
Volume 83,
Issue 10,
pp. 2970-2977,
05/15/1994
Copyright © 1994 by The American Society of Hematology
