Uckun F M, Song C W
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Health Sciences Center, Minneapolis.
Blood. 1993 Mar 1;81(5):1323-32.
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.
采用白血病祖细胞（LPC）集落分析法，分析了27例免疫分型为CD2-CD5-CD7-CD19+slg- B系急性淋巴细胞白血病（ALL）患儿的原代克隆形成性母细胞的辐射敏感性。使用单击中靶及细胞存活的线性二次模型的计算机程序，为每位患者构建原代克隆形成性母细胞（即LPC）的辐射存活曲线。D0值范围为49至891 cGy（中位数为239 cGy；平均值±标准误为307±44 cGy），α值范围为0.000至2.047 Gy-1（中位数为0.156 Gy-1；平均值±标准误为0.284±0.078 Gy-1）。根据性别、年龄、诊断时白细胞计数（WBC）、原代骨髓母细胞的接种效率及免疫表型将患者分组。患者的性别、年龄、诊断时的WBC或体外接种效率与辐射抗性均无关。值得注意的是，具有CD19+CD24-CD34+复合免疫表型（I期B细胞前体[BCP]）患者的新鲜分离的原代克隆形成性母细胞的D0值比具有CD19+CD24+CD34+（II期BCP）或CD19+CD24+CD34-（III期BCP）免疫表型患者的高2.2倍（P = 0.005），α值低3.4倍（P = 0.05）。CD24-原代克隆形成性母细胞的相对值表明其具有更高的内在辐射抗性。此外，CD19+CD24-CD34+免疫表型具有更大的抗辐射部分。仅60%的CD19+CD24+CD34+和33%的CD19+CD24+CD34-病例的克隆形成性母细胞α≤0.2，而100%的CD19+CD24-CD34+病例的克隆形成性母细胞α≤0.2。此外，已建立的CD19+CD24- B系ALL细胞系的克隆形成性母细胞比CD19+CD24+ B系ALL细胞系对辐射的抗性明显更强。值得注意的是，足以诱导CD24- B系ALL细胞凋亡的辐射剂量高于能够诱导CD24+ B系ALL细胞凋亡的剂量。因此，B系ALL中CD24表面抗原表达的缺失与原代克隆形成性母细胞水平的内在辐射抗性相关。
