Correlation between leukemic cell retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate and response to therapy.
Correlation between leukemic cell retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate and response to therapy.
复制标题
白血病细胞保留 1-β-D-阿拉伯呋喃糖基胞嘧啶 5-三磷酸与治疗反应之间的相关性。
作者：
Y. Rustum;H. Preisler
本文研究了白血病成髓细胞对1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）的磷酸化和1-β-D-阿拉伯呋喃糖基胞嘧啶三磷酸（ara-CTP）的胞内滞留与患者对ara-C和蒽环类药物治疗反应的关系。不同患者间ara-CTP的初始形成量和4 h细胞内残留量存在定量差异，根据这些差异，可将患者分为2个亚组：白血病细胞残留≥36%的13例患者和白血病细胞残留≤ 19% ara-CTP 9 s的15例患者。在高保留组的13名患者中，11名获得完全缓解。11例患者中有7例在55+至129+周时保持完全缓解。15例ara-CTP保留率≤19%的患者中有9例获得完全缓解。其中8例患者在11至92周之间复发，1例患者在58+周时仍处于缓解状态。该组的中位缓解持续时间为28周，而对于高保留，它已经超过63周。这些数据表明，尽管这些患者在临床上被诊断为急性髓细胞白血病并以相同的方式治疗，但他们的细胞代谢阿糖胞苷的方式不同。数据表明，急性髓细胞白血病细胞的ara-CTP体外形成和保留与接受ara-C作为其缓解诱导和维持治疗的一部分的患者的缓解持续时间之间存在显著相关性。
Abstract The relationship between the phosphorylation of 1-β-d-arabinofuranosylcytosine (ara-C) and intracellular retention of 1-β-d-arabinofuranosylcytosine triphosphate (ara-CTP) in vitro by leukemic myeloblasts and the response of patients to treatment with ara-C and anthracycline was studied. There were quantitative differences between patients in the amount of ara-CTP initially formed and that retained intracellularly at 4 hr. On the basis of these differences, the patients could be placed into 2 subgroups: those 13 patients whose leukemic cell retention was ≥36% and the remaining 15 patients whose leukemic cells retained ≤19% ara-CTP9s. Of the 13 patients in the high-retention group, 11 attained complete remission. Seven of the 11 patients remain in complete remission at 55+ to 129+ weeks. Nine of 15 patients whose ara-CTP retention was ≤19% attained complete remission. Eight of these patients have relapsed between 11 and 92 weeks, with a single patient remaining in remission at 58+ weeks. The median remission duration for this group was 28 weeks, while for the high retention it has already exceeded 63 weeks. These data indicate that, although these patients are clinically diagnosed as acute myelocytic leukemia and treated in an identical manner, their cells metabolize ara-C differently. The data demonstrate a significant correlation between ara-CTP formation and retention in vitro by acute myelocytic leukemia cells and the duration of remission of patients receiving ara-C as part of their remission induction and maintenance therapy.