Absence of GenomicIkaros/IKZF1Deletions in Pediatric B-Precursor Acute Lymphoblastic Leukemia.
Here we report the results of gene expression analyses using multiple probesets aimed at determining the incidence ofIkaros/IKZF1deletions in pediatric B-precursor acute lymphoblastic leukemia (BPL). Primary leukemia cells from 122 Philadelphia chromosome (Ph)+BPL patients and 237 Ph-BPL patients as well as normal hematopoietic cells from 74 normal non-leukemic bone marrow specimens were organized according to expression levels ofIKZF1transcripts utilizing two-way hierarchical clustering technique to identify specimens with lowIKZF1expression for the 10 probesets interrogating Exons 1 through 4 and Exon 8. Our analysis demonstrated no changes in expression that would be expected from homozygous or heterozygous deletions ofIKZF1in primary leukemic cells. Similar results were obtained in gene expression analysis of primary leukemic cells from 20 Ph+positive and 155 Ph-BPL patients in a validation dataset. Taken together, our gene expression analyses in 534 pediatric BPL cases, including 142 cases with Ph+BPL, contradict previous reports that were based on SNP array data and suggested that Ph+pediatric BPL is characterized by a high frequency of homozygous or heterozygousIKZF1deletions. Further, exon-specific genomic PCR analysis of primary leukemia cells from 21 high-risk pediatric BPL patients and 11 standard-risk pediatric BPL patients, and 8 patients with infant BPL did not show any evidence for homozygousIKZF1locus deletions. Nor was there any evidence for homozygous or heterozygous intragenicIKZF1deletions.
Systems Immunobiology Laboratory, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA 90027 ; Department of Biology and Bioinformatics Program, Gustavus Adolphus College, 800 W College Avenue, St. Peter, MN 56082.
Sanjive
S
Qazi
Systems Immunobiology Laboratory, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA 90027.
Hong
H
Ma
Systems Immunobiology Laboratory, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA 90027 ; Department of Biology and Bioinformatics Program, Gustavus Adolphus College, 800 W College Avenue, St. Peter, MN 56082 ; Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
Fatih M
FM
Uckun