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Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may
be explained by sensitivity to antimetabolites and other drugs: results of
an in vitro study
GJ Kaspers, LA Smets, R Pieters, CH Van Zantwijk, ER Van Wering and AJ Veerman
Department of Pediatrics, Free University Hospital, Amsterdam, The
Netherlands.
DNA hyperdiploidy is a favorable prognostic factor in childhood acute
lymphoblastic leukemia (ALL). The explanation for this prognostic
significance is largely unknown. We have studied whether DNA ploidy was
related to cellular resistance to 12 drugs, assessed with the methyl-
thiazol-tetrazolium assay, in samples of 74 children with common (CD10+
precursor B-cell) ALL. Sixteen patients had hyperdiploid ALL cells and 58
patients had nonhyperdiploid ALL cells. Hyperdiploid ALL cells were more
sensitive to mercaptopurine (median, 9.0-fold; P = .000003), to thioguanine
(1.4-fold; P = .023), to cytarabine (1.8-fold; P = .016), and to
I-asparaginase (19.5-fold; P = .022) than were nonhyperdiploid ALL cells.
In contrast, these two ploidy groups did not differ significantly in
resistance to prednisolone, dexamethasone, vincristine, vindesine,
daunorubicin, doxorubicin, mitoxantrone, and teniposide. The percentage of
S-phase cells was higher (P = .05) in the hyperdiploid ALL samples (median,
8.5%) than in the nonhyperdiploid ALL samples (median, 5.7%). However, the
percentage of cells in S-phase was not significantly related to in vitro
drug resistance. We conclude that the favorable prognosis associated with
DNA hyperdiploidy in childhood common ALL may be explained by a relative
sensitivity of hyperdiploid common ALL cells to antimetabolites, especially
to mercaptopurine and to I-asparaginase.
Volume 85,
Issue 3,
pp. 751-756,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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