Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: Enzymological and clinical aspects

Brouwer, C, Vermunt-de Koning, DGM, Trueworthy, RC, ter Riet, PGJH, Duley, JA, Trijbels, FJM, Hoogerbrugge, PM, Bokkerink, JPM, van Wering, ER and De Abreu, RA (2006) Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: Enzymological and clinical aspects. Pediatric Blood & Cancer, 46 4: 434-438. doi:10.1002/pbc.20452


Author Brouwer, C
Vermunt-de Koning, DGM
Trueworthy, RC
ter Riet, PGJH
Duley, JA
Trijbels, FJM
Hoogerbrugge, PM
Bokkerink, JPM
van Wering, ER
De Abreu, RA
Title Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: Enzymological and clinical aspects
Journal name Pediatric Blood & Cancer   Check publisher's open access policy
ISSN 1545-5009
Publication date 2006-01-01
Year available 2006
Sub-type Article (original research)
DOI 10.1002/pbc.20452
Open Access Status Not yet assessed
Volume 46
Issue 4
Start page 434
End page 438
Total pages 5
Place of publication Hoboken
Publisher Wiley-liss
Language eng
Abstract Background Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.205) catalyzes the rate-limiting step in guanine nucleotide biosynthesis, and may play an important role in treatment of patients with antipurines. Methods. We used an HPLC method to measure the IMPDH activity in peripheral blood and bone marrow mononuclear cells (MNC). IMPDH activities were determined in children who were diagnosed with and treated for acute lymphoblastic leukemia (ALL), and in a group of control children. Results. The median IMPDH activity for control children was 350 pmol/10(6) pMNC/hr (range 97-896; n = 47). No gender or age differences were observed. IMPDH activity at diagnosis of ALL was correlated with the percentage of peripheral blood lymphoblasts (r = 0.474; P < 0.001; n = 71). The median IMPDH activity at diagnosis was 410 pmol/10(6) pMNC/hr (range 40-2009; n = 76), significantly higher than for controls (P = 0.012). IMPDH activity significantly decreased after induction treatment, and during treatment with methotrexate (MTX) infusions (median 174 pmol/10(6) pMNC/hr; range 52-516; n = 21). The activity remained low during maintenance treatment with 6-mercaptopurine (6MP) and MTX, at a significantly lower level than for controls (P < 0.004). One year after cessation of treatment IMPDH activity returned to normal values. Conclusion. The decrease of IMPDH activity at remission of ALL seems to be at least partly due to the eradication of lymphoblasts with the type 2 isoform of the enzyme.
Keyword Oncology
Hematology
Pediatrics
acute lymphoblastic leukemia
inosine monophosphate dehydrogenase
purine enzymes
6-mercaptopurine
Imp Dehydrogenase
Childhood
Recovery
Proliferation
Chemotherapy
Therapy
Cdnas
Q-Index Code C1
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Pharmacy Publications
 
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