IMMATURE AND DIFFERENTIATED NEOPLASTIC POPULATIONS IN ACUTE LYMPHOID LEUKEMIA OF CHILDHOOD - BIOLOGICAL AND CLINICAL IMPLICATIONS

Despite significant improvement in the therapy for acute lymphoid leuk emia (ALL) of childhood, approximately 30% of patients relapse. Unfort unately, since no successful treatment for recurrent disease has been developed, the majority of these patients die. Recently, we presented evidence consistent with the presence of a limited program of differen tiation in B-precursor ALL that is reminiscent of normal B-cell develo pment. We found that ALL cell populations consist of both a subpopulat ion of progenitors with the immunophenotype of normal B-cell precursor s that has self-renewal capability and a second subpopulation with a m ore mature early B-cell immunophenotype that is without self-renewal c apability but can proliferate to a limited extent. In our recent studi es we were able to grow the progenitor cells in the ALL blast colony a ssay and establish their leukemic origin using the polymerase chain re action. Our results suggest that these progenitors are the cells that sustain the disease. We hypothesize that these cells may remain quiesc ent, for a time, and either eventually die or regain proliferative cap ability and cause relapse. Further studies aimed both at detecting res idual ALL and determining changes in their biology may provide an unde rstanding of the mechanisms of relapse in this disease.