Hyperdiploid acute lymphoblastic leukemia with 51 to 65 chromosomes: A distinct biological entity with a marked propensity to undergo apoptosis

To determine the cellular basis for the excellent clinical outcome of hyper diploid acute lymphoblastic leukemia (ALL), defined by a modal chromosome n umber of 51 to 65, we assessed the growth potential of leukemic cells from 129 children with newly diagnosed ALL. Flow cytometric analysis was used to compare leukemic cell recoveries at the beginning and at the end of 7-day cultures on allogeneic bone marrow-derived stromal layers. The median perce ntage of cell recovery after culture was 91% (range, <1% to 550%). Among th e 25 hyperdiploid cases, only two had cell recoveries above the median valu e, compared with 63 of 104 cases with different ploidies (P < .001); 21 had recoveries within the first quartile, in contrast to only 12 of the 104 ot her cases. Cell recoveries in the 16 cases with duplications of chromosomes 4 and 10, a feature previously associated with a superior outcome, were al l within the first quartile. Flow cytometric studies indicated that rapid i nduction of apoptosis was the underlying cause of low cell recoveries in ca ses with hyperdiploidy. The demise of hyperdiploid cells on stroma was not due to failure to adhere with stromal elements (as shown by electron micros copy) or to deficiencies of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-6, I L-7, IL-11, stem-cell factor, interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-a), or to combinations of these cytokines. Inactivation o f IL-4, IFN-alpha and TNF-alpha, which if secreted by stromal layers could he toxic to ALL cells, failed to improve the survival of hyperdiploid blast s. We conclude that leukemic cells bearing 51 to 65 chromosomes have a mark ed propensity to undergo apoptosis. The stringent survival requirements of these cells, together with their potentially higher sensitivity to antileuk emic drugs, may well account for the high cure rates achieved in patients w ith this form of ALL. (C) 1999 by The American Society of Hematology.