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


CONCLUSIONS
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.
Brouwer
Connie
C
Department of Pediatric Hemato-Oncology, University Medical Center St. Radboud, HB Nijmegen, The Netherlands.
Vermunt-de Koning
Diana G M
DG
Trueworthy
Robert C
RC
Ter Riet
Patricia G J H
PG
Duley
John A
JA
Trijbels
Frans J M
FJ
Hoogerbrugge
Peter M
PM
Bökkerink
Jos P M
JP
van Wering
Elisabeth R
ER
De Abreu
Ronney A
RA
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007168:IMP Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy
D007168:IMP Dehydrogenase