Analysis of the immunoglobulin heavy chain gene of secondary diffuse large B-cell lymphoma that subsequently developed in four cases with B-cell chronic lymphocytic leukemia or lymphoplasmacytoid lymphoma (Richter syndrome)

The immunoglobulin heavy chain gene (IgH gene) was analysed in four cases of B-cell Richter syndrome, in order to determine whether a secondary diffuse large B-cell lymphoma (DLBCL) could arise from the same clone as the initial B-cell chronic lymphocytic leukemia (B-CLL) and lymphoplasmacytoid lymphoma (LPL) or be a de novo event, and whether secondary DLBCL shows an intraclonal microheterogeneity. Both the initial B-CLL and secondary DLBCL in two cases expressed CD5 antigen. Both samples of the initial B-CLL or LPL and the secondary DLBCL in three cases were examined for comparison. The polymerase chain reaction-amplified IgH gene of secondary DLBCL in two cases (CD5+ case and CD5− case) were different from those of the initial B-CLL, revealing a new malignant clone. The other case (CD5−) showed that secondary DLBCL had a sequence identical to the initial LPL, indicating the same clonal origin. The variable region of the IgH gene of secondary DLBCL (CD5+ two cases and CD5− two cases) exhibited a 0.5–9.0% somatic mutation range and no intraclonal microheterogeneity.