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Frequency and prognostic significance of HRX rearrangements in infant acute
lymphoblastic leukemia: a Pediatric Oncology Group study
JE Rubnitz, MP Link, JJ Shuster, AJ Carroll, N Hakami, LS Frankel, DJ Pullen and ML Cleary
Department of Pediatrics, Stanford University School of Medicine, CA
94305-5324.
Chromosome band 11q23, the location of the HRX gene, is a site of recurrent
translocations in human malignancies. Infants with acute lymphoblastic
leukemia (ALL) commonly have 11q23 translocations and have an especially
poor prognosis despite intensive chemotherapy. We analyzed 96 cases of
infant ALL treated on three consecutive Pediatric Oncology Group protocols
to determine the frequency and prognostic significance of molecular
rearrangements of HRX. Overall, 78 cases (81%) had HRX rearrangements
detected by Southern blot analysis performed with a single HRX cDNA probe,
whereas 18 cases (19%) had germline HRX. Of the 78 cases with HRX
rearrangements, only 50 had abnormalities of 11q23 detected
cytogenetically. Molecular abnormalities of HRX were associated with early
treatment failure and a very poor outcome. Estimated event-free survival
for patients with HRX rearrangements was 19% (SE, 7%) at 3 years, compared
with 46% (SE, 17%) for patients with germline HRX (P = .033 by the
two-sided logrank test). Therefore, infants with ALL and molecular
abnormalities of HRX represent a group with an extremely high rate of
failure who clearly need innovative or experimental treatment. Furthermore,
cytogenetic analysis alone failed to detected 36% of HRX rearrangements,
suggesting that molecular analysis be performed on all infants with ALL to
identify this group of high-risk patients.
Volume 84,
Issue 2,
pp. 570-573,
07/15/1994
Copyright © 1994 by The American Society of Hematology
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