Premium
Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: Enzymological and clinical aspects
Author(s) -
Brouwer Connie,
Vermuntde Koning Diana G.M.,
Trueworthy Robert C.,
ter Riet Patricia G.J.H.,
Duley John A.,
Trijbels Frans J.M.,
Hoogerbrugge Peter M.,
Bökkerink Jos P.M.,
van Wering Elisabeth R.,
De Abreu Ronney A.
Publication year - 2006
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20452
Subject(s) - imp dehydrogenase , medicine , inosine , lymphoblast , mercaptopurine , peripheral blood mononuclear cell , inosine monophosphate , leukemia , acute lymphocytic leukemia , pharmacology , nucleotide , lymphoblastic leukemia , in vitro , biochemistry , transplantation , cell culture , chemistry , biology , adenosine , gene , mycophenolic acid , genetics
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. Pediatr Blood Cancer 2006, 46:434–438. © 2005 Wiley‐Liss, Inc.