Presence of more than two rearranged immunoglobulin heavy-chain genes in adult precursor B-cell acute lymphoblastic leukemia

Abstract

We examined the configuration of the immunoglobulin genes in the leukemic blast cell DNA of 20 adults with precursor B-cell acute lymphoblastic leukemia (ALL), treated according to the BMFT protocol. Sixteen of 20 (80%) patients expressed HLA-DR antigens and lacked detectable T-cell antigens. Eleven of the 20 patients (55%) were positive for the CD10 antigen and therefore classified as common ALL. Six patients were classified by immunological phenotyping as null-ALL (30%). Three patients (15%) expressed both immature B-cell markers CD19, CD22, or CD24 and myelomonocytic markers CDw65 or CD15, suggesting precursor B-ALL with cross-lineage expression of myeloid markers. In 18 of the 20 patients (90%), rearrangements and/or deletions of the immunoglobulin heavy-chain (IgH) gene locus were found. In none of the patients was a light-chain gene rearrangement observed. Two patients (10%) had a rearrangement of one allele for the J beta 1 gene region of the TCR-beta gene. In four patients (20%) more than two hybridizing bands for the IgH genes were detected. Two of these four patients with multiple hybridizing bands for the IgH genes had a t (4;11) translocation. Two of five patients with the t (4;11) translocation co-expressed both B-cell antigens and the myeloid antigens CD15 or CDw65. No correlation was found between the immunophenotype of the ALL and the arrangement pattern of their IgH genes. Kaplan-Meier plot analysis revealed no significant difference between adult precursor B-ALL patients with monoclonal or oligoclonal IgH gene rearrangements and their disease-free survival rates.

Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

“…Kitchingman et al 18 detected hyperdiploidy in 9/18 pediatric patients with oligoclonality, and 8 of them presented polysomy of chromosome 14. Forestier et al, 35 Moreira et al 36 and Schardt et al, 30 in studies on children and adults, respectively, found no alterations of chromosome 14. In the present study, the karyotype was analyzed in 7/15 cases with bi/oligoclonality, and changes in chromosome 14 were detected in 2 cases, one of them with polysomy and the other with structural alterations, i.e.…”

“…33,38 The presence of bi/ oligoclonality or clonal evolution, although relatively frequent, is mostly associated with the same D-JH sequence, with events in the rearranged VH gene being more common (VH to VH, VH to D-JH). 30,33,37,38,41 Bi/oligoclonality in a rearranged IgH gene has been detected in 20 to 50% of B-lineage acute lymphoblastic leukemia cases in studies by Southern blot 17,18,[30][31][32] and in 10-40% of cases by polymerase chain reaction. 20,31,33,34 The explanation for the difference in oligoclonality findings may be due to the fact that incomplete D-J rearrangements can be detected by southern blot but not by polymerase chain reaction.…”