Matthews Christine, Catherwood Mark A, Morris T C M, Kettle Paul J, Drake Mary B, Gilmore William S, Alexander H Denis
Department of Haematology, Belfast City Hospital, Belfast, UK.
Eur J Haematol. 2006 Oct;77(4):309-17. doi: 10.1111/j.1600-0609.2006.00707.x. Epub 2006 Jul 19.
Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated.
Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively.
Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001).
A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.
血清胸苷激酶（TK）水平已被证明与包括慢性淋巴细胞白血病（CLL）在内的多种恶性肿瘤的生存率相关。本研究旨在调查初诊和既往诊断的Binet A期患者中TK水平与其他预后标志物之间的关联。此外，还研究了使用血清TK测量来识别由IgV(H)突变状态、基因使用情况和染色体畸变所定义的疾病亚类。
纳入91例CLL患者。使用放射酶法测量血清TK水平。使用BIOMED-2引物和方案确定IgV(H)突变状态和V(H)基因使用情况。通过间期荧光原位杂交（FISH）检测复发性染色体异常。流式细胞术和逆转录聚合酶链反应（RT-PCR）分别测定CD38和Zap-70的表达。
与IgV(H)突变患者相比，IgV(H)未突变患者的血清TK水平显著更高（P < 0.001）。CD38和Zap-70阳性患者（分别为P = 0.004，P < 0.001）、淋巴细胞倍增时间（LDT）短的患者（P = 0.044）以及预后不良或中等的染色体畸变患者（P < 0.001）中也发现TK水平升高。
TK水平>8.5 U/L最能识别疾病进展的患者。TK水平升高可识别那些在诊断时根据各种生物学标志物（突变的IgV(H)、预后良好的染色体畸变、Zap-70(-)和CD38(-)）被归类为预后良好亚组但随后出现疾病进展的患者。此外，无论突变状态如何，使用V(H)3-21基因患者的TK水平都较高，并且在所有研究的亚类中，随着疾病进展，血清TK测量仍具有预测能力。
