Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.
In this study, we show that all-trans retinoic acid (ATRA) treatment leads to a rapid decrease in telomerase activity, which was associated with the reduction in myeloblasts and occurs before the appearance of myelocytes, in a patient with acute promyelocytic leukemia (APL). Microarray analysis by ATRA treatment for 48 hr in peripheral blood mononuclear cells (in vivo) and in cultured bone marrow mononuclear cells (in vitro) from a patient with APL revealed upregulation of CD11b, CD11c, CCAAT enhancer binding protein epsilon, Rb1, Mad, and tumor necrosis factor-related genes; and downregulation of hTERT, c-Myc, WT1, bcl-2, and eukaryotic translation elongation factor 1alpha2. The results might offer the potential to define the molecular mechanism underlying ATRA-induced granulocytic differentiation in patients with APL, and provide clues to identify novel molecular therapeutic targets.
Akiyama
Masaharu
M
Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan. makiyama@jikei.ac.jp
Yamada
Osamu
O
Yanagisawa
Takaaki
T
Fujisawa
Kohji
K
Eto
Yoshikatsu
Y
Yamada
Hisashi
H
D000943:Antigens, Differentiation / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002648:Child; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects* / Q000235:genetics; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D014212:Tretinoin; D012313:RNA; D019098:Telomerase