Radivoyevitch Tomas, Kozubek Stanislav, Sachs Rainer K
Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Radiat Res. 2002 Jan;157(1):106-9. doi: 10.1667/0033-7587(2002)157[0106:trocml]2.0.co;2.
Chronic myeloid leukemia (CML) is caused by a BCR-ABL chromosome translocation in a primitive hematopoietic stem cell. The number of hematopoietic stem cells in the body is thus a major factor in CML risk. Evidence suggests that the number of hematopoietic stem cells in the body is only loosely regulated, having a broad "dead-band" of physiologically acceptable values. The existence of a dead-band is important, because it would imply that low levels of hematopoietic stem cell killing can be permanent; i.e., it would imply that low doses of ionizing radiation can cause permanent reductions in the total number of CML target cells and thus permanent reductions in the subsequent risk of spontaneous CML. Such reductions in risk could be substantial if hematopoietic stem cells are also hypersensitive to radiation killing at low dose. Our calculations indicate that, due to dead-band hematopoietic stem cell control, if hematopoietic stem cells are as hypersensitive to killing at low doses as epithelial cells, reductions in the spontaneous CML risk could exceed the low-dose risks of induced CML; i.e., the net lifetime CML risk could have a U-shaped dose-response curve.
慢性髓性白血病（CML）由原始造血干细胞中的BCR-ABL染色体易位引起。因此，体内造血干细胞的数量是CML风险的一个主要因素。有证据表明，体内造血干细胞的数量仅受到宽松调节，具有一个宽泛的生理可接受值“死区”。死区的存在很重要，因为这意味着低水平的造血干细胞杀伤可能是永久性的；也就是说，这意味着低剂量的电离辐射可导致CML靶细胞总数的永久性减少，从而使随后自发发生CML的风险永久性降低。如果造血干细胞在低剂量时对辐射杀伤也高度敏感，那么这种风险降低可能会很显著。我们的计算表明，由于造血干细胞控制存在死区，如果造血干细胞在低剂量时对杀伤的敏感性与上皮细胞一样，那么自发CML风险的降低可能会超过诱导性CML的低剂量风险；即，CML的终身净风险可能呈U形剂量反应曲线。
