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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1188-1194
NEOPLASIA
Loss of heterozygosity in childhood de novo acute
myelogenous leukemia
David A. Sweetser,
Chien-Shing Chen,
Adam A. Blomberg,
David A. Flowers,
Patricia C. Galipeau,
Michael T. Barrett,
Nyla A. Heerema,
Jonathan Buckley,
William G. Woods,
Irwin D. Bernstein, and
Brian J. Reid
From the Fred Hutchinson Cancer Research Center,
Seattle, WA; the Departments of Medicine and Genetics, University
of Washington, Seattle, WA; Parker Hughes Institute, St Paul,
MN; the University of Southern California/Norris Comprehensive
Cancer Center, Los Angeles, CA; and the South Carolina Cancer Center,
Columbia, SC.
A genome-wide screening for loss of heterozygosity (LOH), a marker
for possible involvement of tumor suppressor genes, was conducted in 53 children with de novo acute myelogenous leukemia (AML). A total of 177 highly polymorphic microsatellite repeat markers were used in
locus-specific polymerase chain reactions. This comprehensive
allelotyping employed flow-sorted cells from diagnostic samples and
whole-genome amplification of DNA from small, highly purified samples.
Nineteen regions of allelic loss in 17 patients (32%) were detected on
chromosome arms 1q, 3q, 5q, 7q (n = 2), 9q (n = 4), 11p (n = 2),
12p (n = 3), 13q (n = 2), 16q, 19q, and Y. The study revealed a
degree of allelic loss underestimated by routine cytogenetic analysis,
which failed to detect 9 of these LOH events. There was no evidence of
LOH by intragenic markers for p53, Nf1, or
CBFA2/AML1. Most lymphocytes lacked the deletions, which
were detected only in the leukemic myeloid blast population. Analysis
of patients' clinical and biologic characteristics indicated that the
presence of LOH was associated with a white blood cell count of
20 × 109/L or higher but was not correlated with
a shorter overall survival. The relatively low rate of LOH observed in
this study compared with findings in solid tumors and in pediatric
acute lymphoblastic leukemia and adult AML suggests that tumor
suppressor genes are either infrequently involved in the development of
pediatric de novo AML or are inactivated by such means as methylation
and point mutations. Additional study is needed to determine whether
these regions of LOH harbor tumor suppressor genes and whether specific regions of LOH correlate with clinical characteristics.
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