The effects of STI571 on antigen presentation of dendritic cells generated from patients with chronic myelogenous leukemia.
Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation.
Sato
Naoko
N
First Department of Internal Medicine, Niigata University School of Medicine, Niigata City, Japan. nao24@maple.ocn.ne.jp
Narita
Miwako
M
Takahashi
Masuhiro
M
Yagisawa
Kumiko
K
Liu
Aichun
A
Abe
Takashi
T
Nikkuni
Kohji
K
Furukawa
Tatsuo
T
Toba
Ken
K
Aizawa
Yoshifusa
Y
D017951:Antigen Presentation / Q000187:drug effects*; D015703:Antigens, CD / Q000378:metabolism; D001549:Benzamides; D002478:Cells, Cultured; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015342:DNA Probes; D003713:Dendritic Cells / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D017403:In Situ Hybridization; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D014178:Translocation, Genetic
D015703:Antigens, CD; D001549:Benzamides; D015342:DNA Probes; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl