Biochemical correlates of the differential sensitivity of subtypes of human
leukemia to deoxyadenosine and deoxycoformycin
SS Matsumoto, AL Yu, LC Bleeker, B Bakay, FH Kung and WL Nyhan
Leukemic cells incubated in vitro with 2'-deoxyadenosine (dAdo) plus an
inhibitor of adenosine deaminase, 2'-deoxy-coformycin (DCF), show different
metabolic responses depending on the histologic and immunologic type of the
leukemia. Leukemic cells were obtained from 54 patients with acute
lymphoblastic leukemia (ALL), 9 with myeloid or nonlymphoblastic leukemia,
3 with chronic lymphocytic leukemia (CLL), and 3 with lymphoma. There was a
wide variation in the LD50, the concentration of dAdo that caused 50%
inhibition of the incorporation of 3H-thymidine into cells in the presence
of 20 microM DCF. T-cell leukemia specimens were much more sensitive to
dAdo than were specimens of pre-B-ALL and null-ALL. In leukemic cells that
had been incubated with 14C-dAdo plus DCF, a good correlation was observed
between the LD50 and the ratio of 14C-deoxyATP to ATP (correlation
coefficient for the fit to a hyperbola = 0.853). The accumulation of
deoxyATP by the leukemic cell specimens was correlated best with the
activity of ecto- ATPase, less well with cytoplasmic 5'-nucleotidase and
deoxyadenosine kinase, and poorly with adenosine deaminase and
ecto-5'-nucleotidase. The clinical response to DCF therapy of a patient
with T-ALL and another with pre-B-ALL was consistent with the in vitro
metabolic response of their cells to DCF and dAdo.
Volume 60,
Issue 5,
pp. 1096-1102,
11/01/1982
Copyright © 1982 by The American Society of Hematology
