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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 315-320
Hyperdiploid Acute Lymphoblastic Leukemia With 51 to 65 Chromosomes: A Distinct Biological Entity With a Marked Propensity
to Undergo Apoptosis
Chikako Ito,
Masa-aki Kumagai,
Atsushi Manabe,
Elaine Coustan-Smith,
Susana C. Raimondi,
Frederick G. Behm,
K. Gopal Murti,
Jeffrey E. Rubnitz,
Ching-Hon Pui, and
Dario Campana
From the Departments of Hematology-Oncology, Pathology and Laboratory
Medicine, and Virology and Molecular Biology, St Jude Children's
Research Hospital, Memphis; and the University of Tennessee Memphis
College of Medicine, Memphis, TN.
To determine the cellular basis for the excellent clinical outcome
of hyperdiploid acute lymphoblastic leukemia (ALL), defined by a modal
chromosome number 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 percentage of cell recovery
after culture was 91% (range, <1% to 550%). Among the 25 hyperdiploid cases, only two had cell recoveries above the median
value, 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 other cases. Cell recoveries in the 16 cases with
duplications of chromosomes 4 and 10, a feature previously associated
with a superior outcome, were all within the first quartile. Flow
cytometric studies indicated that rapid induction of apoptosis was the
underlying cause of low cell recoveries in cases with hyperdiploidy.
The demise of hyperdiploid cells on stroma was not due to failure to
adhere with stromal elements (as shown by electron microscopy) or to
deficiencies of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-6, IL-7,
IL-11, stem-cell factor, interferon- (IFN-), tumor necrosis
factor- (TNF-), or to combinations of these cytokines.
Inactivation of IL-4, IFN- and TNF-, which if secreted by stromal
layers could be toxic to ALL cells, failed to improve the survival of
hyperdiploid blasts. We conclude that leukemic cells bearing 51 to 65 chromosomes have a marked propensity to undergo apoptosis. The
stringent survival requirements of these cells, together with their
potentially higher sensitivity to antileukemic drugs, may well account
for the high cure rates achieved in patients with this form of ALL.
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