Analyses of phenotype and genotype in acute lymphoblastic leukemias at first presentation and in relapse.

As a clue to the cellular origin of leukemic populations in relapse we analyzed 11 cases of acute lymphoblastic leukemia (ALL) by immunological and molecular genetic approaches. Blast cells obtained from both initial diagnosis and relapse were immunophenotyped using a variety of monoclonal antibodies; simultaneously we hybridized Southern blots of respective cell samples to immunoglobulin (Ig) heavy and light chain as well as to T-cell receptor beta-chain (T beta) sequences. While similar phenotypes were observed in both states of nine cases, comparison of Ig gene rearrangements revealed clonal variations, ie, appearance of an evoluted or novel leukemic cell clone in relapse beside identical leukemic populations in both states. One pre-T (ALL) patient, presenting with germline configuration of T beta gene sequences at diagnosis, exhibited a rearrangement of T beta gene sequences in recurrent disease. Another patient displayed T-ALL phenotype and T beta gene rearrangement at diagnosis but relapsed with a very immature phenotype and germline configuration for T beta sequences. Our results emphasize the value of molecular analyses in order to unravel the nature of leukemic relapse.