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HRX involvement in de novo and secondary leukemias with diverse chromosome
11q23 abnormalities [see comments]
SP Hunger, DC Tkachuk, MD Amylon, MP Link, AJ Carroll, JL Welborn, CL Willman and ML Cleary
Department of Pathology, Stanford University School of Medicine 94305-
5324.
Chromosome band 11q23 is a site of recurrent translocations and
interstitial deletions in human leukemias. Recent studies have shown that
the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19
after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create
fusion genes encoding proteins with structural features of chimeric
transcription factors. In this report, we show structural alterations of
HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias
with cytogenetically diverse 11q23 abnormalities. The sole case that lacked
HRX rearrangements was a t(11;17)-acute myeloid leukemia with
French-American-British M3-like morphology. We also analyzed 10 secondary
leukemias that arose after therapy with topoisomerase II inhibitors and
found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2
with unsuccessful karyotypes. In total, we observed HRX rearrangements in
35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27,
7p15, 9p21-24, 15q15, 16p13, and two 19p13 sites). All breakpoints
localized to an 8-kb region that encompassed exons 5-11 of HRX, suggesting
that fusion proteins containing similar portions of HRX may be consistently
created in leukemias with 11q23 abnormalities. We conclude that alteration
of HRX is a recurrent pathogenetic event in leukemias with 11q23
aberrations involving many potential partners in a variety of settings
including acute myeloid leukemia, acute lymphoblastic leukemia, chronic
myelogenous leukemia in blast crisis, and topoisomerase II inhibitor-
induced secondary leukemias of both the myeloid and lymphoid lineages.
Volume 81,
Issue 12,
pp. 3197-3203,
06/15/1993
Copyright © 1993 by The American Society of Hematology
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