Selective up-regulation of type II inosine 5'-monophosphate dehydrogenase messenger RNA expression in human leukemias

Cancer Res. 1991 Aug 1;51(15):3886-90.


The discovery of isozymes (types I and II) of IMP dehydrogenase (IMPDH; EC, the rate-limiting enzyme of de novo GTP biosynthesis, has attracted attention as a possible novel approach to cancer diagnosis and selective tumor cell chemotherapy. To elucidate differences in expression and regulation of the two IMPDH isozymes, we examined the steady-state levels of these mRNAs in various types of leukemic cells from patients. Northern blot analysis revealed that type II IMPDH was more active transcriptionally (1.5- to 5.1-fold) in all the leukemic cells examined than in normal lymphocytes, whereas type I expression was similar. The increased expression of type II mRNA in leukemic cells was closely linked with the increase in total IMPDH activity (r = 0.92). When leukemic cells from a patient with chronic granulocytic leukemia in blast crisis were separated into blast-rich and mature leukocyte-rich fractions, the expression of type II mRNA correlated positively with the population of immature leukemic cells, whereas type I expression was unchanged. Treatment of leukemic blasts with 12-O-tetradecanoyl-phorbol-13-acetate for 5 days resulted in a 90% decrease in the expression of type II mRNA with macrophage-like differentiation, while the expression of type I mRNA was relatively stable. These observations suggest that expression of type II IMPDH is stringently linked with immature characteristics of leukemic cells; thus, it should be a selective target for antileukemic chemotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Differentiation / physiology
  • DNA / genetics
  • Gene Expression Regulation, Enzymologic / physiology
  • Gene Expression Regulation, Leukemic / physiology
  • Hematopoietic System / cytology
  • Hematopoietic System / enzymology
  • Humans
  • IMP Dehydrogenase / genetics
  • IMP Dehydrogenase / metabolism*
  • IMP Dehydrogenase / physiology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Isoenzymes / physiology
  • Leukemia / enzymology*
  • Leukemia / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Up-Regulation / physiology*


  • Isoenzymes
  • RNA, Messenger
  • DNA
  • IMP Dehydrogenase