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The HRX proto-oncogene product is widely expressed in human tissues and
localizes to nuclear structures
LH Butler, R Slany, X Cui, ML Cleary and DY Mason
University Department of Cellular Science, John Radcliffe Hospital, Oxford,
UK.
Chromosomal rearrangement of the HRX (MLL, ALL-1, Htrx) gene situated at
chromosome band 11q23 is one of the most frequent genetic changes in infant
leukemias of myeloid and lymphoid lineage and in treatment- induced
secondary leukemias. The HRX gene codes for a predicted 431-kD protein that
shows significant homology to the Drosophila trithorax protein, an Hox
epigenetic regulator. Typically, the region encoding the HRX gene is
rearranged, mostly in reciprocal translocations with a number of partners,
resulting in a range of fusion genes. However, this is not the only
abnormality affecting HRX because partial duplication of the gene, as well
as interstitial deletions, can occur. Despite extensive studies of HRX at
the genetic level, the protein products of the HRX gene and their patterns
of expression in normal and leukemic cells remain uncharacterized. In this
study we analyzed the distribution and localization of HRX proteins in cell
lines and human tissues, using both polyclonal and monoclonal antibodies.
The specificity of these reagents was confirmed using cells transfected
with the HRX-ENL fusion gene. Western blot analyses of protein extracts
from cells carrying the t(11;19) and t(4;11) translocations showed HRX
chimeric proteins whose migrations corresponded to the sizes predicted from
analyses of translocation-induced fusion mRNAs expressed by the derivative
11 chromosomes. Immunocytochemical analysis showed a punctate distribution
of wild-type and chimeric HRX proteins within cell nuclei, suggesting that
HRX localizes to nuclear structures in cells with and without 11q23
translocations. Nuclear staining was found in the majority of tissues
studied with the strongest reactivity in cerebral cortex, kidney, thyroid,
and lymphoid tissues. Thus, HRX is widely expressed in most cell types
including hematopoietic cells, a finding that precludes an
immunocytochemical approach for diagnosis of leukemias bearing 11q23
structural abnormalities.
Volume 89,
Issue 9,
pp. 3361-3370,
05/01/1997
Copyright © 1997 by The American Society of Hematology
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