PMID- 10978780
OWN - NLM
STAT- MEDLINE
DCOM- 20001020
LR  - 20190826
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 24
IP  - 9
DP  - 2000 Sep
TI  - Differentiation induction in non-lymphocytic leukemia cells upon treatment with 
      mycophenolate mofetil.
PG  - 761-8
AB  - Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction 
      of guanine nucleotide biosynthesis and has been implicated in the reaction of 
      cell growth and differentiation. We investigated the ability of mycophenolate 
      mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and 
      U937 leukemic cells as well as in fresh leukemia cells from patients with 
      non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the 
      intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and 
      functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and 
      U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b 
      and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These 
      changes became evident when the intracellular GTP levels decreased to 
      approximately 20-30% of the untreated control level and were abrogated by the 
      addition of guanosine. In the fresh leukemic cells, differentiation induction was 
      shown in the cells derived from seven of 13 patients. The fresh leukemia cells 
      responding to mycophenolate mofetil revealed significant higher positivity to 
      CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP 
      levels after treatment compared to the non-responding cells. These findings 
      suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 
      cells and some fresh leukemia cells with moderate tendency to maturation, by 
      causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could 
      be a promising differentiation inducer in vivo.
FAU - Inai, K
AU  - Inai K
AD  - First Department of Internal Medicine, Fukui Medical University, School of 
      Medicine, Fukui, Japan.
FAU - Tsutani, H
AU  - Tsutani H
FAU - Yamauchi, T
AU  - Yamauchi T
FAU - Fukushima, T
AU  - Fukushima T
FAU - Iwasaki, H
AU  - Iwasaki H
FAU - Imamura, S
AU  - Imamura S
FAU - Wano, Y
AU  - Wano Y
FAU - Nemoto, Y
AU  - Nemoto Y
FAU - Naiki, H
AU  - Naiki H
FAU - Ueda, T
AU  - Ueda T
LA  - eng
PT  - Journal Article
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Antineoplastic Agents)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Female
MH  - HL-60 Cells
MH  - Humans
MH  - Leukemia, Myeloid/*pathology
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/*analogs & derivatives/pharmacology
MH  - Myelodysplastic Syndromes/*pathology
MH  - Tumor Cells, Cultured
MH  - U937 Cells
EDAT- 2000/09/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/09 11:00
PHST- 2000/09/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/09 11:00 [entrez]
AID - S0145-2126(00)00045-X [pii]
AID - 10.1016/s0145-2126(00)00045-x [doi]
PST - ppublish
SO  - Leuk Res. 2000 Sep;24(9):761-8. doi: 10.1016/s0145-2126(00)00045-x.