Characterization of clonal immunoglobulin heavy chain and I cell receptor gamma gene rearrangements during progression of childhood acute lymphoblastic leukemia.
Instability of antigen receptor gene rearrangements during progression of acute lymphoblastic leukemia (ALL) has important implications for polymerase chain reaction (PCR)-based techniques using these genes for the detection of minimal residual disease (MRD). Antigen receptor gene instability may lead to false negative results in bone marrow samples taken during remission. Utilizing the PCR and consensus primers for rearranged immunoglobulin heavy chain (IgH) and T cell receptor gamma (TCR gamma) gene sequences, we analyzed the bone marrow samples at diagnosis and first relapse for 37 children with ALL. The incidence of clonal evolution at the IgH locus was 9/33 (27%) and at the TCR gamma locus 1/15 (7%). In four of the nine patients with clonal evolution at the IgH locus, the sequence at relapse retained the diversity and joining region (D-N-J) sequences from diagnosis. Patients with clonal evolution were characterized by a higher incidence of more than one IgH PCR band at diagnosis and by late relapse (> 18 months from diagnosis). These results suggest that, where possible, patients with more than one IgH PCR rearrangement at diagnosis should be monitored using another antigen receptor gene, such as TCR gamma, since evolution for this gene was found to be a rare event. By combining this approach with a strategy directed at the more stable D-N-J region of the IgH gene, MRD false negativity would have occurred in less than 10% of patients in the present study.
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual / Q000175:diagnosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013997:Time Factors
D017931:DNA Primers; D004273:DNA, Neoplasm; D016692:Receptors, Antigen, T-Cell, gamma-delta