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.