Loss of heterozygosity in childhood de novo acute myelogenous leukemia

A genome-wide screening for loss of heterozygosity (LOH), a marker for poss ible involvement of tumor suppressor genes, was conducted in 53 children wi th de novo acute myelogenous leukemia (AML). A total of 177 highly polymorp hic microsatellite repeat markers were used in locus-specific polymerase ch ain reactions. This comprehensive allelotyping employed flow-sorted cells f rom diagnostic samples and whole-genome amplification of DNA from small, hi ghly 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 de gree of allelic loss underestimated by routine cytogenetic analysis, which failed to detect 9 of these LOH events. There was no evidence of LOH by int ragenic markers for p53, Nf1, or CBFA2/AML1. Most lymphocytes lacked the de letions, 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 x 1 0(9)/L or higher but was not correlated with a shorter overall survival. Th e relatively low rate of LOH observed in this study compared with findings in solid tumors and in pediatric acute lymphoblastic, leukemia and adult AM L suggests that tumor suppressor genes are either infrequently involved in the development of pediatric de novo AML or are inactivated by such means a s methylation and point mutations. Additional study is needed to determine whether these regions of LOH harbor tumor suppressor genes and whether spec ific regions of LOH correlate with clinical characteristics.