Clonal immunoglobulin gene rearrangements in chronic lymphocytic leukemia: a correlative study

Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for immunoglobulin gene and T-cell receptor gene rearrangements. Immunoglobulin heavy chain gene rearrangements were demonstrable in 41 cases. One rearrangement of the T-cell receptor beta chain gene was detected. Quantification of the relative intensities of germline and rearranged DNA bands suggests that a significant component of the lymphocytosis may be due to cell populations other than the malignant clonal population, particularly in earlier stages of the disease. A direct relationship was found between severity of disease and the relative amount of clonal immunoglobulin heavy chain gene rearrangement. Preliminary data for 12 patients followed sequentially indicated that clinical deteriorations or improvements are reflected in an increase or decrease, respectively, in the proportion of cells with rearranged immunoglobulin genes. Change in the relative proportion of cells with germline versus rearranged genes may provide an additional useful criterion for staging CLL, for more precisely defining the abnormal lymphocyte population, and for monitoring progression of the disease and efficacy of treatment.