TY - JOUR
T1 - Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia
T2 - Enzymological and clinical aspects
AU - Brouwer, Connie
AU - Vermunt-De Koning, Diana G.M.
AU - Trueworthy, Robert C.
AU - Ter Riet, Patricia G.J.H.
AU - Duley, John A.
AU - Trijbels, Frans J.M.
AU - Hoogerbrugge, Peter M.
AU - Bökkerink, Jos P.M.
AU - Van Wering, Elisabeth R.
AU - De Abreu, Ronney A.
PY - 2006/4
Y1 - 2006/4
N2 - 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/106 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/106 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/106 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.
AB - 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/106 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/106 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/106 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.
KW - 6-mercaptopurine
KW - Acute lymphoblastic leukemia
KW - Inosine monophosphate dehydrogenase
KW - Purine enzymes
UR - http://www.scopus.com/inward/record.url?scp=33644697201&partnerID=8YFLogxK
U2 - 10.1002/pbc.20452
DO - 10.1002/pbc.20452
M3 - Article
C2 - 16333815
AN - SCOPUS:33644697201
SN - 1545-5009
VL - 46
SP - 434
EP - 438
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 4
ER -