In vitro and in vivo radiation resistance associated with CD3 surface
antigen expression in T-lineage acute lymphoblastic leukemia
FM Uckun, NK Ramsay, KG Waddick, W Jaszcz, M Chandan-Langlie, V Obuz, R Haake, K Gajl-Peczalska, JH Kersey and CW Song
Section of Cancer and Leukemia Biology, University of Minnesota Health
Sciences Center, Minneapolis.
The radiobiologic features of primary clonogenic blasts (referred to also
as T-lineage leukemic progenitor cells) from newly diagnosed and relapsed
T-lineage acute lymphoblastic leukemia (ALL) patients were analyzed.
Intrinsic radiation sensitivity differed substantially among primary
clonogenic blasts from 34 newly diagnosed patients. The mean D0 (37% dose
slope), SF2 (surviving fraction at 200 cGy), and alpha values (initial
slope of the survival curve) were 141 +/- 15 cGy, 0.31 +/- 0.04, and 0.630
+/- 0.093 Gy-1, respectively. Among newly diagnosed cases, nine had SF2
values of greater than or equal to 0.50 and alpha values of less than or
equal to 0.2 Gy-1, consistent with a marked intrinsic radiation resistance
at the level of clonogenic blasts using the multitarget and linear
quadratic models of cell survival. Of these nine radiation resistant cases,
seven were CD3+. Furthermore, the mean D0 (162 +/- 20.8 cGy) and SF2 (0.377
+/- 0.057) values for the 20 CD3+ cases were significantly higher than the
D0 (108.6 +/- 18.2 cGy) and SF2 (0.204 +/- 0.051) values for the 14 CD3-
cases (P less than or equal to .05). Thus, clonogenic blasts from CD3+
newly diagnosed T- lineage ALL patients were more resistant to radiation
than clonogenic blasts from CD3- newly diagnosed T-lineage ALL patients.
Nineteen T- lineage ALL patients received autologous bone marrow
transplants during complete remission. Pretransplant conditioning consisted
of total body irradiation (TBI) combined with high-dose chemotherapy.
Primary clonogenic blasts from patients who relapsed after bone marrow
transplantation (BMT) displayed a particularly high degree of intrinsic
radiation resistance with a mean D0 value of 333 cGy and an alpha value of
0.112 Gy-1. The expression of CD3 antigen appeared to predict the outcome
of relapsed T-lineage ALL patients undergoing autologous BMT after TBI plus
high-dose chemotherapy. The Kaplan-Meier estimates and standard errors of
the probability of remaining in remission after BMT were 60% +/- 22% (mean
relapse - free interval = 1.6 +/- 0.7 years) for CD3- patients and 0% +/-
0% (mean relapse - free interval = 0.2 +/- 0.0 years) for CD3+ patients (P
= .002). Furthermore, the mean percentage of CD3-positive leukemic marrow
blasts at presentation or relapse before BMT was significantly lower than
the mean percentage of CD3- positive leukemic marrow blasts at relapse
after BMT. Notably, in cultured leukemic bone marrow specimens from newly
diagnosed as well as relapsed patients, colony blasts surviving in vitro
radiation expressed CD3 more vividly than did colony blasts in unirradiated
cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 78,
Issue 11,
pp. 2945-2955,
12/01/1991
Copyright © 1991 by The American Society of Hematology
