PERSISTENCE OF SELF-RENEWING LEUKEMIA-CELL PROGENITORS DURING REMISSION IN CHILDREN WITH B-PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA

No effective therapy is available for the majority of the 30-40% of ch ildren with acute lymphoblastic leukemia (ALL) who relapse. Since the morphologically undetectable, or occult, leukemia cells that persist d uring remission originate from the clone present at diagnosis, may als o have both the capability to sustain the disease and to give rise to relapse, we are evaluating a method of identifying them. We have combi ned, for the first time, an ALL blast colony assay (BCA) and the polym erase chain reaction (PCR) to isolate residual leukemia cells in remis sion bone marrow aspirate specimens from eight patients with B-precurs or ALL during early continuation therapy. We found colony-forming leuk emia cells with in vitro self-renewal capability that survived chemoth erapy for 15 months after diagnosis in all sequential specimens from t hese patients. To verify the leukemic nature of these cells their DNA was amplified by PCR and the product directly sequenced. In every case , the V(H)DJ(H) sequence observed at diagnosis was found. None of the patients relapsed during this early phase of their treatment, consiste nt with the observation that patients with B-precursor ALL experience recurrence late in their course. Since it is possible that some of the se persistent leukemia cells belong to the leukemia progenitor cell po pulation that sustains the disease, the study of them could provide th e means to determine the mechanisms of relapse.