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Title: Radiation resistance of primary clonogenic blasts from children with acute lymphoblastic leukemia

Journal Article · · International Journal of Radiation Oncology, Biology and Physics; (United States)
 [1]; ;  [2]
  1. Univ. of Minnesota Health Sciences Center, Minneapolis, MN (United States) Childrens Cancer Group, Arcadia, CA (United States)
  2. Univ. of Minnesota Health Sciences Center, Minneapolis, MN (United States)

Detailed comparative analyses of the radiation sensitivity of primary clonogenic blasts from children with acute lymphoblastic leukemia (ALL) were performed to achieve a better understanding of clinical radiation resistance in ALL. The radiation sensitivity of primary clonogenic blasts from 74 children with newly diagnosed ALL was analyzed using leukemic progenitor cell (LPC) assays. Primary bone marrow blasts from all 74 patients were exposed to ionizing radiation and subsequently assayed for LPC-derived blast colony formation. Radiation survival curves of LPC were constructed for each of the newly diagnosed patients using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. A marked interpatient variation in intrinsic radiation sensitivity was observed between LPC populations. The SF[sub 2] values ranged from 0.01 to 1.00. Patients were divided into groups according to their sex, age, WBC at diagnosis, cell cycle distribution of leukemic blasts, and immunophenotype. Only immunophenotype provided a significant correlation with the intrinsic radiation sensitivity of LPC. Patients with B-lineage ALL had higher SF[sub 2] and smaller [alpha] values than T-lineage ALL patients, consistent with greater intrinsic radiation resistance at the level of LPC. Notably, 43% of B-lineage ALL cases, but only 27% of T-lineage ALL cases had LPC with SF[sub 2] [ge] 0.5. Similarly, 66% of B-lineage ALL cases, but only 37% of T-lineage ALL cases had LPC with [alpha] values [le] 0.4 Gy[sup [minus]1]. Combining the two indicators of radiation resistance, they found that only 34% of the B-lineage ALL patients had none of the two parameters in the respective critical regions, while 63% of the T-lineage patients had none. In multivariate analyses, the immunophenotypic B-lineage affiliation was the only significant predictor of radiation resistance at the level of LPC. 42 refs., 1 fig., 2 tabs.

OSTI ID:
7066215
Journal Information:
International Journal of Radiation Oncology, Biology and Physics; (United States), Vol. 27:4; ISSN 0360-3016
Country of Publication:
United States
Language:
English