title: Alterations in immunoglobulin or T cell receptor gene rearrangement at relapse: involvement of 11q23 and changes in immunophenotype.
abstract: We studied the organization of immunoglobulin (Ig) genes and the beta-chain gene of the T cell receptor (TCR) along with the clinical features, immunophenotypes, and karyotypes of 14 children with acute leukemia at diagnosis and relapse. The median time to relapse was 23 months. Eleven children had identical gene rearrangement patterns at diagnosis and relapse. All three patients whose blast cells showed variations in gene rearrangement patterns between diagnosis and relapase also demonstrated a change in the immunophenotype: one from cALLA+ to cALLA- B precursor cell ALL; one from T-ALL to AML; and one showed a marked increase in myeloid characteristics at relapse. Blast cells from these three patients at relapse showed the presence of chromosomal translocations involving 11q23; for two patients, this involved replacement of the original karyotype. We conclude that while most relapses are the result of reemergence of the original clone, new clones that differ in immunophenotype, karyotype, and gene rearrangement are occasionally present at relapse. Relapses may also occur in which the original clone has undergone major changes in gene expression and arrangement of the Ig heavy chain genes in the absence of karyotypic replacement.
authors.affiliation: Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: N J
authors.initials: NJ
authors.lastname: Bunin
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: J
authors.initials: J
authors.lastname: Mirro
authors.forename: F G
authors.initials: FG
authors.lastname: Behm
authors.forename: R
authors.initials: R
authors.lastname: Goorha
authors.forename: G R
authors.initials: GR
authors.lastname: Kitchingman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics* / Q000276:immunology; D008297:Male; D012008:Recurrence; D014178:Translocation, Genetic