Clonal analysis of B-cell leukemias and lymphomas using the polymerase chain reaction for the third complementarity determining region of the IgH gene: a study of 75 cases from Nagasaki Japan

Using semi-nested polymerase chain reaction (PCR), we examined 75 Japanese cases of hematologic malignancies with B-cell antigens including 25 common acute lymphoblastic leukemia (ALL), 13 chronic lymphocytic leukemia (CLL), 28 B-cell malignant lymphoma(B-ML), 2 hairy cell leukemia (HCL), 7 acute my elogenous leukemia with B-cell antigens (AML-B), and 23 controls, When ampl ified products were analysed by a standard polyacrylamide gel electrophores is, the sensitivity for detection of clonal IgH rearrangements in each grou p of ALL, CLL, B-ML, HCL, and AML-B was 88%, 92.3%, 71.4%,100%, and 57.1%, respectively, with an overall sensitivity of 80.0%. There were no false pos itive results in any of the control samples. Single strand conformation pol ymorphism (SSCP) analysis of the amplified products gave rise, to a much gr eater sensitivity, up to 84% overall. The false negative samples were mainl y encountered in B-ML with SmIgC and non-Ig, suggesting miss-annealing betw een the primers used and the template DNA because of somatic hypermutation of IgH genes in such clones. This indicates that PCR analysis is very usefu l in detecting the clonal IgH rearrangements in B-cell malignancies, especi ally in ALL and CLL, but not in B-ML corresponding to neoplasms originating from pre-germinal center naive B-cells.