Musto P, Bodenizza C, Falcone A, D'Arena G, Scalzulli P, Perla G, Modoni S, Parlatore L, Valvano M R, Carotenuto M
Division of Haematology, IRCCS Casa Sollievo della Sofferenza Hospital, S. Giovanni Rotondo, Italy.
Br J Haematol. 1995 May;90(1):125-30. doi: 10.1111/j.1365-2141.1995.tb03390.x.
The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.
本研究旨在评估胸苷激酶血清水平（s-TK）这一增殖活性间接标志物在骨髓增生异常综合征（MDS）中可能的预后相关性。采用放射酶法对90例MDS患者（22例难治性贫血，RA；17例伴有环形铁粒幼细胞的RA，RARS；21例伴有原始细胞增多的RA，RAEB；15例转变中的RAEB，RAEB-T；15例慢性粒单核细胞白血病，CMMoL）的s-TK水平进行监测。诊断时测得的平均s-TK水平（U/微升），RA为11.9±12.6，RARS为11.4±13.6，RAEB为19.9±28.4，RAEB-T为39.6±34.3，CMMoL为77.7±69.7（正常值<5 U/微升）。除与乳酸脱氢酶存在微弱关系外，初始s-TK值与其他临床或实验室参数，如年龄、血红蛋白、白细胞或血小板计数、骨髓原始细胞百分比之间均未发现相关性。通过ROC统计分析选择的截断水平s-TK>38 U/微升的MDS患者，其生存期显著短于s-TK<38 U/微升的患者（分别为8.2个月和37.4个月；P<0.0001）。特别是，s-TK>38 U/微升的患者中有17/21（8l%）发生急性髓系白血病（AML）转变，而诊断时水平较低的患者中这一比例为9/69（13%）（P<0.0001），与FAB亚型无关。高s-TK水平对于初始值正常的患者在疾病过程中预测AML演变也很有用。多变量分析证实了s-TK对总生存期和急性转变风险的独立预后价值。我们得出结论，s-TK可能是MDS的一个重要预后因素，与AML的发生密切相关。
