Aul C, Gattermann N, Germing U, Winkelmann M, Heyll A, Runde V, Schneider W
Department of Internal Medicine, Heinrich Heine University, Düsseldorf, Germany.
Cancer. 1994 Jan 15;73(2):322-7. doi: 10.1002/1097-0142(19940115)73:2<322::aid-cncr2820730215>3.0.co;2-e.
Previous studies have shown that serum levels of deoxythymidine kinase (sTK) provide useful prognostic information in various malignancies, such as Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma, and acute myeloid leukemia (AML).
Using a radioenzyme assay, the authors determined sTK in 146 patients with primary myelodysplastic syndromes (MDS). Morphologic subtypes were refractory anemia (RA) in 18 patients, RA with ring sideroblasts (RARS) in 24, RA with excess of blasts (RAEB) in 41, RAEB in transformation (RAEB/T) in 29, and chronic myelomonocytic leukemia (CMML) in 34.
Enzyme levels ranged from 1.1 to 829 U/microliters. One hundred fifteen (79%) patients had elevated sTK levels (more than 5 U/microliters) at the time of diagnosis. In advanced stages of MDS (RAEB, CMML, and RAEB/T) enzyme activities were higher than in early stages (RA and RARS) (P < 0.05). However, sTK levels were not correlated with the percentage of medullary blast cells. Among other parameters tested, the best correlation with sTK was found for serum lactate dehydrogenase (LDH) activity (r = 0.29; P < 0.0005). As shown by life table analysis, sTK activity at diagnosis provided useful information regarding the prognosis of patients. For patients with sTK levels of less than 10 U/microliters, actuarial survival after 2 years was 65%, compared with 33% for those with enzyme values of 10 U/microliters or greater. The 5-year cumulative survival rates were 34% and 14%, respectively (P < 0.0005). However, sTK levels at diagnosis were not useful for predicting transformation to AML. Nine of 61 (15%) patients with sTK of less than 10 U/microliters had AML develop, whereas 15 of 57 (26%) patients with sTK of 10 U/microliters or greater had disease progress to acute leukemia (chi-square, 1.64; P = 0.2).
Considering the lack of correlation with bone marrow blasts, the authors conclude that increased sTK levels in MDS are primarily attributable to intramedullary destruction of hematopoietic precursors and do not reflect the leukemic blast cell burden. This appears similar to the ineffective hematopoiesis of vitamin B12 deficiency, which is associated with elevated levels of sTK and LDH. The data suggest that sTK is a prognostic parameter that can be used to predict the survival of patients with MDS. However, multivariate analysis shows that the predictive value of sTK is not superior to that of LDH.
既往研究表明，血清脱氧胸苷激酶（sTK）水平可为多种恶性肿瘤提供有用的预后信息，如霍奇金病、非霍奇金淋巴瘤、多发性骨髓瘤和急性髓细胞白血病（AML）。
作者采用放射酶法测定了146例原发性骨髓增生异常综合征（MDS）患者的sTK水平。形态学亚型包括18例难治性贫血（RA）、24例伴有环形铁粒幼细胞的难治性贫血（RARS）、41例伴有过多原始细胞的难治性贫血（RAEB）、29例转化中的RAEB（RAEB/T）以及34例慢性粒单核细胞白血病（CMML）。
酶水平范围为1.1至829 U/微升。115例（79%）患者在诊断时sTK水平升高（超过5 U/微升）。在MDS的晚期（RAEB、CMML和RAEB/T），酶活性高于早期（RA和RARS）（P < 0.05）。然而，sTK水平与骨髓原始细胞百分比无关。在测试的其他参数中，发现与sTK相关性最好的是血清乳酸脱氢酶（LDH）活性（r = 0.29；P < 0.0005）。生存表分析显示，诊断时的sTK活性可为患者的预后提供有用信息。sTK水平低于10 U/微升的患者，2年后的精算生存率为65%，而酶值为10 U/微升或更高的患者为33%。5年累积生存率分别为34%和14%（P < 0.0005）。然而，诊断时的sTK水平对预测转化为AML并无帮助。61例sTK低于10 U/微升的患者中有9例（15%）发生了AML，而57例sTK为10 U/微升或更高的患者中有15例（26%）疾病进展为急性白血病（卡方检验，1.64；P = 0.2）。
考虑到与骨髓原始细胞缺乏相关性，作者得出结论，MDS中sTK水平升高主要归因于造血前体细胞的髓内破坏，并不反映白血病原始细胞负荷。这似乎类似于维生素B12缺乏导致的无效造血，后者与sTK和LDH水平升高有关。数据表明，sTK是一个可用于预测MDS患者生存的预后参数。然而，多变量分析显示，sTK的预测价值并不优于LDH。
