Hypoxanthine‐guanine phosphoribosyl‐transferase in childhood leukemia: Relation with immunophenotype, in vitro drug resistance and clinical prognosis
Hypoxanthine‐guanine phosphoribosyl‐transferase in childhood leukemia: Relation with immunophenotype, in vitro drug resistance and clinical prognosis
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儿童白血病中的次黄嘌呤鸟嘌呤磷酸核糖转移酶：与免疫表型、体外耐药性和临床预后的关系
DOI：
10.1002/ijc.2910510208
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发表时间：
1992
影响因子：
6.4
通讯作者：
'. A.J.P.vEERMAN
中科院分区：
文献类型：
--
作者：
'. R.PIETERS;'. D.R.HUBMANS;'. A.H.LOONEN;G. Peters;K. Hahlen;van der;DOES;Den;Berg;R. E.;van Wering;'. A.J.P.vEERMAN
次黄嘌呤鸟嘌呤磷酸核糖基转移酶(HGPRT)负责6-巯基嘌呤和6-硫代鸟嘌呤(6-TG)向细胞毒核苷酸的转化，其活性降低可能导致在实验白血病系统中对这些硫嘌呤产生抗药性。这一机制的临床意义尚不清楚。对83例初治急性淋巴细胞白血病(ALL)患儿进行了HGPRT活性测定，并探讨了HGPRT活性与硫唑嘌呤耐药的关系。用放射化学法测定HGPRT活性，用四甲基偶氮唑盐比色法测定细胞对6-甘油三酯的体外抗性。T-ALL组HGPRT水平显著低于B系ALL组，不同分化阶段的B系ALL组HGPRT水平差异无统计学意义。HGPRT活性与白细胞计数(WBC)呈负相关。在WBC和Lt；50×109/i的CALL和Pre-B-ALL患者中，HGPRT低的患者预后明显差于HGPRT高的患者。两组患者的WBC、年龄、性别、器官肿大和分化程度相似。在CALL和前B-ALL患者中，HGPRT活性与体外6-TG抵抗无相关性。T-ALL患者对6-TG的耐受性并不比CALL和Pre-B-ALL患者更高。6例复发患者的HGPRT活性均未见下降。我们的结论是：(A)HGPRT在T-ALL中低于B-ALL，并且在B-ALL的序贯分化阶段中是恒定的；(B)HGPRT活性与肿瘤负荷成反比；(C)在B-ALL前体中，HGPRT活性低与较差的预后相关，但这不能用硫代嘌呤耐药来解释，因为(D)HGPRT活性与体外6-TG耐药无关。
Decreased activity of hypoxanthine‐guanine phosphoribosyltransferase (HGPRT), responsible for the conversion of 6‐mercaptopurine and 6‐thioguanine (6‐TG) to their cytotoxic nucleotides, may cause resistance to these thiopurines in experimental leukemic systems. The clinical significance of this mechanism is as yet unclear. In 83 children with untreated acute lymphoblastic leukemia (ALL), we determined the prognostic value of HGPRT activity and the relation between HGPRT activity and resistance to thiopurines. HGPRT activity was determined radiochemically; in vitro resistance to 6‐TG with the MTT assay. HGPRT level was significantly lower in T‐ALL than in B‐lineage ALL; no differences were found between sequential differentiation stages of B‐lineage ALL. HGPRT activity was inversely related to the white‐blood‐cell count (WBC). Among patients with cALL and pre‐B‐ALL with WBC < 50 × 109/I, cases with a low HGPRT had a significantly poorer prognosis than those with a high HGPRT. WBC, age, sex, organomegaly and differentiation stage were comparable in both patient groups. No correlation was found between HGPRT activity and in vitro 6‐TG resistance in cALL and pre‐B‐ALL patients. T‐ALL cases were not more 6‐TG‐resistant than cALL and pre‐B‐ALL cases. Cells from 6 relapsed ALL cases did not show decreased HGPRT activity. We conclude that: (a) HGPRT is lower in T‐ than in B‐lineage ALL and is constant in sequential differentiation stages of B‐lineage ALL; (b) HGPRT activity is inversely related to tumor load; (c) low HGPRT activities are correlated with a poorer prognosis in precursor B‐ALL but this cannot be explained by thiopurine resistance because (d) there is no relation between HGPRT activity and in vitro 6‐TG resistance.
影响因子：
2.6
作者：
Evans,WE;Petros,WP;Relling,MV;Crom,WR;Madden,T;Rodman,JH;Sunderland,M
通讯作者：
Sunderland,M