Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.
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- c mu- 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.
Pieters
R
R
Free University Hospital, Department of Pediatrics, Amsterdam, The Netherlands.
Huismans
D R
DR
Loonen
A H
AH
Peters
G J
GJ
Hählen
K
K
van der Does-van den Berg
A
A
van Wering
E R
ER
Veerman
A J
AJ
D015720:5'-Nucleotidase / Q000032:analysis*; D000135:Acid Phosphatase / Q000032:analysis*; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology*; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D015122:Mercaptopurine; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D015720:5'-Nucleotidase; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin