Purine metabolism in childhood acute lymphoblastic leukemia: biochemical markers for diagnosis and chemotherapy.
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.
D015720:5'-Nucleotidase; D000659:AMP Deaminase / Q000378:metabolism; D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000293:Adolescent; D001853:Bone Marrow / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007223:Infant; D007945:Leukemia, Lymphoid / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D009708:Nucleotidases / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D011687:Purines / Q000378:metabolism*
D011687:Purines; D011683:Purine-Nucleoside Phosphorylase; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D000248:Adenosine Kinase; D000263:Adenylate Kinase; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000659:AMP Deaminase