Detection of immunoglobulin heavy chain genes rearrangements in B-cell leukemias, lymphomas, multiple myelomas, monoclonal and polyclonal gammopathies.
Polymerase chain reaction (PCR) based assays were found to be a realistic alternative to Southern blot hybridization for the assessment of clonal immunoglobulin heavy chain gene rearrangements. However, a comparison of the different PCR based studies reveals considerable variation in experimental design and marked differences in the reported results. This study compared different single- and double-step PCR assays relying on various FR3, FR2, FR1 and JH based primers for the detection of B cell clonality in acute lymphoblastic leukemias (ALL), non-Hodgkin's-lymphoma (NHL), multiple myeloma (MM), monoclonal gammopathies of unknown significance (MGUS) and three polyclonal gammopathies (PG). The highest monoclonality rate was observed using seminested CDR-III region amplification. This method achieved a monoclonal product in 6 of 13 pro-B ALL 21 of 29 c-ALL, 7 of 8 pre-B-ALL, 18 of 21 B-ALL, 14 of 17 B-NHL (intermediate or high grade) with bone marrow involvement, 0 of 9 B-NHL without bone marrow involvement, 9 of 9 low grade B-NHL (immunocytoma and including chronic lymphocytic leucemia), 13 of 19 MM, 2 of 9 MGUS, and 0 of 3 PG. Additional monoclonality was detected with nested CDR I PCR in 1 pro-B-ALL, 1 c-ALL, and 2 MM. CDR III IgH PCR has been confirmed as an efficient method for determining clonality in B-cell neoplasias. Some additional monoclonal products can be seen with CDR I-based PCR. Detection of monoclonality depends on the maturation grade of the neoplastic B-cell population.
Gleissner
B
B
University Hospital Benjamin Franklin, Department of Hematology, Oncology and Transfusion Medicine, Free University of Berlin, Germany.
Maurer
J
J
Thiel
E
E
D001854:Bone Marrow Cells; D018929:Cell Culture Techniques; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions; D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase / Q000592:standards; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007160:Immunoproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015448:Leukemia, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010265:Paraproteinemias / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D011379:Prognosis; D014407:Tumor Cells, Cultured
D022801:Complementarity Determining Regions; D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D004259:DNA-Directed DNA Polymerase