Intrinsic radiation resistance of primary clonogenic blasts from children with newly diagnosed B-cell precursor acute lymphoblastic leukemia

Abstract

The radiation sensitivity of primary clonogenic blasts from 44 children with newly diagnosed B-cell precursor acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. The derived values for SF2 (surviving fraction at 200 cGy) and α (initial slope of radiation survival curves constructed according to the linear quadratic model) indicated a marked interpatient heterogeneity in intrinsic radiation sensitivity of LPC populations. The SF2 values ranged from 0.01 to 1.00 (median = 0.430; mean±SE = 0.47±0.04), and the α values ranged from 0.000 to 3.272 Gy-1 (median = 0.280 Gy-1; mean±SE = 0.430±0.093 Gy-1). When CD19+ CD34+ versus CD19+ CD34- immunophenotypes were compared, a trend toward higher SF2 and lower α values were observed in LPC from CD34+ patients, consistent with greater radiation resistance. When patients were divided into three approximately equal groups based on increasing levels of CD34 expression, a clear ordering effect was observed indicating that increased CD34 expression levels are associated with significantly higher radiation resistance at the level of B-lineage LPC. The highest CD34 expression group (≥ 75% positivity) had 1.4-fold higher SF2 (P = 0.05) and twofold lower α values (P = 0.06) than the lowest group (< 30% positivity). Furthermore, the CD34 positivity of radiation resistant (α ≤ 0.2 and SF2 ≥ 0.5) B-cell precursor ALL cases was greater than the CD34 positivity of radiation sensitive (α > 0.2 and/or SF2 < 0.5) cases (56±9% versus 34±9%, P = 0.09). Whereas only 6 of 16 (38%) of radiation sensitive cases were CD34+, 11 of 15 (73%) of radiation resistant cases expressed CD34 (P = 0.04). Our results offer new insights into the inherent and/ or acquired radiation resistance of primary clonogenic blasts from B-cell precursor ALL patients.