Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis.
Many reports have described the relationship of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities with the immunological subclasses of acute lymphoblastic leukemia (ALL). The clinical significance of these enzymes in leukemias is not yet completely understood. We performed a study in 83 children with untreated ALL to establish the relationships of ADA and PNP to clinical outcome, in vitro drug resistance and differentiation stage of B-cell lineage ALL. ADA and PNP activities were determined radiochemically. In vitro resistance to 6-thioguanine (6-TG) was determined with the MTT assay. ADA activity was not different between proB- and cALL cases but decreased in the sequential differentiation stages cALL----preB-ALL----B-ALL. The PNP level was not different between the four stages of B-lineage ALL. Patients with cALL/preB ALL with low ADA activities had a significantly poorer probability of survival (p = 0.005) than patients with high ADA levels. Patients with cALL/preB ALL with low PNP activities showed a non-significant trend for a poorer prognosis (0.05 less than p less than 0.10) than patients with a high PNP level. Low ADA and PNP activities were not related to in vitro resistance to 6-TG. We conclude that ADA decreases and PNP remains constant in sequential differentiation stages of B-lineage ALL. Patients with precursor B-lineage ALL with low activities of ADA have a poorer prognosis than those with high activities of these enzymes. No relationship could be detected between ADA or PNP activity and resistance to 6-TG.
Pieters
R
R
Department of Pediatrics, Free University Hospital, 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
D000243:Adenosine Deaminase / Q000097:blood*; D001773:Blood Cells / Q000201:enzymology; D001853:Bone Marrow / Q000201:enzymology; D002454:Cell Differentiation; D002648:Child; D004351:Drug Resistance; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000401:mortality; D011379:Prognosis; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood*; D013866:Thioguanine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D011683:Purine-Nucleoside Phosphorylase; D000243:Adenosine Deaminase; D013866:Thioguanine