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儿童急性淋巴细胞白血病中的嘌呤代谢:诊断和化疗的生化标志物

Purine metabolism in childhood acute lymphoblastic leukemia: biochemical markers for diagnosis and chemotherapy.

作者信息

van Laarhoven J P, Spierenburg G T, Bakkeren J A, Schouten T J, De Bruyn C H, Geerts S J, Schretlen E D

出版信息

Leuk Res. 1983;7(3):407-20. doi: 10.1016/0145-2126(83)90105-4.

DOI:10.1016/0145-2126(83)90105-4
PMID:6310274
Abstract

Adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), 5'nucleotidase (5'NT), ecto-5'NT, hypoxanthine-guanine phosphoribosyltransferase(HGPRT), adenine phosphoribosyltransferase(APRT), adenosine kinase(AK), AMP deaminase (AMPD) and adenylate kinase(AdKin) activities were assayed in leukemic cells from bone marrow and/or peripheral blood of 43 newly diagnosed children with acute lymphoblastic leukemia(ALL). These enzyme activities have been investigated in relation to some immunological markers. ADA activity was higher in E-rosette positive leukemia(E+ ALL), while HGPRT, APRT, PNP, 5'NT, ecto-5'NT and AdKin activities were found to be lower in E+ ALL as compared to E- ALL. In common ALL (cALL) antigen positive leukemia, mean ADA activity was significantly lower as compared to cALL- leukemia, whereas PNP, 5'NT, ecto-5'NT and AdKin activities were significantly higher. cALL cells with cytoplasmic immunoglobulin M(IgM) heavy chains were found to have mean 5'NT activities twice as high as cALL cells lacking cytoplasmic IgM heavy chains. In two patients who had surface immunoglobulins on their cell membranes, low 5'NT activities were found. When measuring enzyme activities after 2-4 days of prednisone monotherapy, only mean ADA and HGPRT activities decreased in non-B, non-T ALL. These decreases were not significant in T-ALL patients. Mean enzyme activities in the leukemic cells of five patients with relapse were comparable to those in newly diagnosed patients, except for 5'NT, which was found to be within the activity range of control peripheral blood lymphocytes. It is concluded that ADA and AdKin activities are suitable as markers for E+ ALL and cALL+ leukemias respectively. 5'NT might help to distinguish between cALL cells having and lacking pre-B characteristics. Since 5'NT activity may also be decreased in B-ALL, it is not suitable as a T-ALL marker. Enzymes of purine metabolism in leukemic relapse need further investigation.

摘要

对43例新诊断的急性淋巴细胞白血病(ALL)患儿骨髓和/或外周血白血病细胞中的腺苷脱氨酶(ADA)、嘌呤核苷磷酸化酶(PNP)、5'-核苷酸酶(5'NT)、胞外5'-核苷酸酶(ecto-5'NT)、次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT)、腺嘌呤磷酸核糖转移酶(APRT)、腺苷激酶(AK)、AMP脱氨酶(AMPD)和腺苷酸激酶(AdKin)活性进行了测定。已针对一些免疫标志物对这些酶活性进行了研究。E玫瑰花结阳性白血病(E+ALL)中的ADA活性较高,而与E-ALL相比,E+ALL中的HGPRT、APRT、PNP、5'NT、ecto-5'NT和AdKin活性较低。在常见ALL(cALL)抗原阳性白血病中,与cALL-白血病相比,平均ADA活性显著降低,而PNP、5'NT、ecto-5'NT和AdKin活性显著升高。发现具有细胞质免疫球蛋白M(IgM)重链的cALL细胞的平均5'NT活性是缺乏细胞质IgM重链的cALL细胞的两倍。在两名细胞膜上有表面免疫球蛋白的患者中,发现5'NT活性较低。在泼尼松单药治疗2-4天后测量酶活性时,非B、非T ALL中仅平均ADA和HGPRT活性降低。这些降低在T-ALL患者中不显著。五例复发患者白血病细胞中的平均酶活性与新诊断患者相当,但5'NT除外,其活性在对照外周血淋巴细胞的活性范围内。结论是,ADA和AdKin活性分别适合作为E+ALL和cALL+白血病的标志物。5'NT可能有助于区分具有和不具有前B细胞特征的cALL细胞。由于B-ALL中5'NT活性也可能降低,因此它不适合作为T-ALL标志物。白血病复发时嘌呤代谢酶需要进一步研究。

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引用本文的文献

1
Biochemical enzyme analysis in acute leukaemia.急性白血病的生化酶分析
J Clin Pathol. 1985 Feb;38(2):117-27. doi: 10.1136/jcp.38.2.117.
2
Enzymes of purine metabolism in lymphoid neoplasms, clinical relevance for treatment with enzyme inhibitors.淋巴肿瘤中嘌呤代谢的酶,酶抑制剂治疗的临床相关性。
Klin Wochenschr. 1988 Jun 1;66(11):467-74. doi: 10.1007/BF01876167.