Oligoclonal immunoglobulin heavy-chain and T-cell receptor delta rearrangements persist in a recurrent acute lymphoblastic leukemia with one immunoglobulin kappa rearrangement as a clonal marker

Acute lymphoblastic leukemias (ALLs) represent the clonal expansion of a ly mphoid precursor cell. Therefore, all cells of an ALL should have identical antigen receptor gene rearrangements. In a patient with diploid ALL of the B-cell precursor immunophenotype, seven different clonal rearrangements of the immunoglobulin heavy-chain genes (IgH) were identified, implying the p resence of oligoclonal populations. All of these rearrangements were only d etectable after a modification of the polymerase chain reaction for the com plementarity determining region of the IgH genes using V-H, gene framework 3 and J(H), consensus primers. Sequence analysis showed that these rearrang ements were completely unrelated to each other. Only two of these rearrange ments were detectable by Southern blot analysis. Quantification and single- cell analysis confirmed the high frequency of these latter two rearrangemen ts, as well as their presence in the same clonal population. The other rear rangements characterized less than 5% of the leukemic population. In additi on, two T-cell receptor V delta 2-D delta 3 (TCR delta) rearrangements were identified, both at a similar frequency. However, they were derived from d ifferent cells. An Ig kappa rearrangement represented the only clonal marke r in this leukemia. All of the Ig and TCR delta rearrangements, with the ex ception of one IgH rearrangement, remained stable throughout the course of the disease. The persistence of such a great number of distinct IgH rearran gements at different quantities within the leukemic population and of the t wo biclonal TCR delta rearrangements is compatible with the presence of a c lonal disease that is defined by the Ig kappa rearrangement.