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Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia
is associated with intrinsic radiation resistance of primary clonogenic
blasts
FM Uckun and CW Song
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis.
The radiation sensitivity of primary clonogenic blasts from 27 children
with immunologically classified CD2-CD5-CD7-CD19+slg- B-lineage acute
lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell
(LPC) colony assays. Radiation survival curves of primary clonogenic blasts
(ie, LPC) were constructed for each patient using computer programs for the
single-hit multitarget as well as the linear quadratic models of cell
survival. The D0 values ranged from 49 to 891 cGy (median, 239 cGy; mean
+/- SE, 307 +/- 44 cGy) and the alpha values ranged from 0.000 to 2.047
Gy-1 (median, 0.156 Gy-1; mean +/- SE, 0.284 +/- 0.078 Gy-1). Patients were
divided into groups according to sex, age, white blood cell count (WBC) at
diagnosis, plating efficiency of primary bone marrow blasts, and
immunophenotype. Patient sex, age, WBC at diagnosis, or in vitro plating
efficiency was not associated with radiation resistance. Notably, freshly
isolated primary clonogenic blasts from patients with a CD19+CD24-CD34+
composite immunophenotype (stage I B-cell precursor [BCP]) had 2.2-fold
higher D0 values (P = .005) and 3.4-fold lower alpha values (P = .05) than
those from patients with a CD19+CD24+CD34+ (stage II BCP) or
CD19+CD24+CD34- (stage III BCP) immunophenotype. The relative values for
CD24- primary clonogenic blasts signify greater intrinsic radiation
resistance. Furthermore, the CD19+CD24-CD34+ immunophenotype had a larger
radiation resistant fraction. Whereas only 60% of CD19+CD24+CD34+ and 33%
of CD19+CD24+CD34- cases had clonogenic blasts with alpha < or = 0.2,
100% of CD19+CD24-CD34+ cases had clonogenic blasts with alpha < or =
0.2. Furthermore, clonogenic blasts from established CD19+CD24- B-lineage
ALL cell lines were significantly more radiation resistant than CD19+CD24+
B-lineage ALL cell lines. Notably, radiation doses sufficient to induce
apoptosis of CD24- B-lineage ALL cells were higher than those capable of
inducing apoptosis in CD24+ B-lineage ALL cells. Thus, the lack of CD24
surface antigen expression in B-lineage ALL is associated with intrinsic
radiation resistance at the level of primary clonogenic blasts.
Volume 81,
Issue 5,
pp. 1323-1332,
03/01/1993
Copyright © 1993 by The American Society of Hematology
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