@article{53faa17f3c8b466fb1ae9345ae1ab971,
title = "Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia",
abstract = "Ecto-5′-nucleotidase (ecto-5′NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5′NT (cyto-5′NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5′NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10 cμ- precursor B-ALL. CD10+ ALL cases with high ecto-5′NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5′NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5′NT and AP activities. We conclude that high ecto-5′NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5′NT and AP activities associated with 6-thiopurine resistance.",
keywords = "5′nucleotidase, IMPase, MTT assay, childhood leukemia, drug resistance, phosphatase, prognosis, purine metabolism, thiopurines",
author = "R. Pieters and Huismans, \{D. R.\} and Loonen, \{A. H.\} and Peters, \{G. J.\} and K. H{\"a}hlen and \{van der Does-van den Berg\}, A. and \{van Wering\}, \{E. R.\} and Veerman, \{A. J.P.\}",
note = "Funding Information: NUCLEOTIDASES catalyze the dephosphorylation of purine nucleotides like GMP, IMP and AMP to their corresponding nucleosides guanosine, inosine and adenosine respectively. Ecto-5'nucleotidase (ecto-5'NT) is localized on the cell membrane with the enzymatic activity facing the external medium. Its function involves extracellular dephosphorylation of nucleotides to which cells are impermeable, into readily transported nucleosides \textbackslash{}[1-5\textbackslash{}]. The intracellular degradation of nucleotides is most probably not regulated by ecto-5'NT but by cytoplasmic 5'NT (cyto-5'NT) and by non-specific phosphatases like acid-and alkaline phosphatases (AP). Cyto-5'NT is biochemically distinguishable from ecto-5'NT \textbackslash{}[6-8\textbackslash{}] because of a different pH optimum (6.0 vs 7.4-9.0 respectively). Also, a\textasciitilde{},fl-methylene adenosine dipho- * Supported by the Dutch Cancer Society (IKA 87-17). Correspondence to: R. Pieters, M.D., Ph.D., M.Sc., Free University Hospital, Department of Pediatrics, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.",
year = "1992",
month = sep,
doi = "10.1016/0145-2126(92)90033-4",
language = "English",
volume = "16",
pages = "873--880",
journal = "Leukemia research",
issn = "0145-2126",
publisher = "Elsevier Ltd.",
number = "9",
}