title: Low p53 expression of acute myelocytic leukemia cells with t(8;21) chromosome abnormality: association with low p14(ARF) expression.
abstract: In this study, the mRNA expression of p14(ARF) in t(8;21)AML cells was found to be significantly lower than acute myelocytic leukemia (AML) cells without t(8;21) chromosome abnormality, which was concordant with previous observation by Linggi et al. that AML1-MTG8 represses the transcription of p14(ARF). Although p53 mRNA expression level of t(8;21)AML cells was not low, p53 protein expression was reduced in t(8;21)AML cells. Genotoxic damage by ionizing radiation did not induce p53 upregulation in t(8;21)AML cells. Since p14(ARF) has been demonstrated to inhibit p53 degradation by binding to MDM2, repression of p14(ARF) expression in t(8;21)AML may facilitate the degradation of p53 by MDM2. Low p14(ARF) in t(8;21)AML may also account for the absence of upregulation of p53 by ionizing radiation. Then, we have shown that p53 expression level was inversely correlated with S/G2/M population of cell cycle in AML cells. Most of the t(8;21)AML are considered to be in p53(low) S/G2/M(high). It is now widely known that formation of AML1-MTG8 by t(8;21) translocation is a very early event in leukemogenesis, and AML1-MTG8 alone might have limited proliferative potential. Then, secondary oncogenic events such as activated receptor tyrosine kinase (like c-kit mutation), is necessary to become full-blown leukemia. Low p53 protein expression and insufficient induction of p53 by genotoxic damage might increase the opportunity to obtain additional oncogenic events, since genome guard function of p53 does not work in t(8;21)AML cells.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Aichi Medical University, 21 Karimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shikami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miwa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Taiichi
authors.initials: T
authors.lastname: Kyo
authors.forename: Isao
authors.initials: I
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Kita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nitta
mesh_terms: D002453:Cell Cycle; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53