Allelotype analysis in relapsed childhood acute lymphoblastic leukemia.
We performed for the first time the allelotype of relapsed childhood acute lymphoblastic leukemia (ALL). A total of 38 cases were screened for loss of heterozygosity (LOH) using 71 markers. In all, 26 (68%) patients showed LOH on at least one chromosomal arm, indicating that LOH is a frequent event at relapse. The most frequent loss was found on chromosomal arm 9p at the p16/INK4a locus (39%). LOH at the TEL gene locus on chromosomal arm 12p also occurred often (25%). Frequent loss was observed on chromosome arms 4q (20%), 6q (21%), and 17q (20%). Sequential analysis (i.e. samples obtained from both initial diagnosis and relapse) shows that some patients (63%) have the identical LOH status at both phases, suggesting the presence of the same clone. Other samples (37%) showed distinct LOH alterations, indicating clonal evolution at relapse. Despite the heterogeneous and complex changes, some shared LOH loci occurred in these matched samples, suggesting that many of the same tumor-suppressor genes are aberrant at both phases. In summary, novel tumor-suppressor genes on chromosome arms 4q, 6q, and 17q, as well as the p16 and TEL genes, have an important role in the relapse of childhood ALL.
Takeuchi
Seisho
S
Department of Medicine, Kochi Medical School, Okohcho, Nankoku, Kochi 783-8505, Japan. takeuti@kochi-ms.ac.jp
Seriu
Taku
T
van Dongen
Jacques J M
JJ
Szczepański
Tomasz
T
Tsukasaki
Kunihiro
K
Takeuchi
Naoko
N
Fermin
Anthony C
AC
Seo
Hiromi
H
Bartram
Claus R
CR
Koeffler
H Phillip
HP
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002894:Chromosomes, Human, Pair 4; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein