Accumulation of γ-globin mRNA and induction of erythroid differentiation after treatment of human leukaemic K562 cells with tallimustine

被引:76
作者
Bianchi, N
Chiarabelli, C
Borgatti, M
Mischiati, C
Fibach, E
Gambari, R
机构
[1] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy
[2] Hadassah Univ Hosp, Dept Haematol, IL-91120 Jerusalem, Israel
[3] Univ Ferrara, Ctr Biotechnol, Lab Dev Pharmacol & Gene Therapy Thalassaemia, I-44100 Ferrara, Italy
关键词
K562; cells; erythroid differentiation; DNA-binding drugs; distamycin; tallimustine;
D O I
10.1046/j.1365-2141.2001.02843.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Human leukaemic K562 cells can be induced in vitro to erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and cisplatin analogues. Differentiation of K562 cells is associated with an increase of expression of embryofetal globin genes, such as the zeta-, epsilon- and gamma -globin genes. The K562 cell line has been proposed as a very useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation stimulating gamma -globin synthesis could be considered for possible use in the therapy of haematological diseases associated with a failure in the expression of normal beta -globin genes, We have analysed the effects of tallimustine and distamycin on cell growth and differentiation of K562 cells. The results demonstrated that tallimustine is a potent inducer, while distamycin is a weak. inducer, of K562 cell erythroid differentiation. Erythroid differentiation was associated with an increase of accumulation of gamma -globin mRNA and of production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition, tallimustine-mediated erythroid induction occurred in the presence of activation of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of gamma -globin gene expression are strongly sustained by the finding that this compound stimulates fetal haemoglobin production in human erythroid precursor cells from normal subjects.
引用
收藏
页码:951 / 961
页数:11
相关论文
共 79 条
  • [1] ALKHATTI A, 1988, BLOOD, V72, P817
  • [2] STRUCTURE + SYNTHESIS OF DISTAMYCIN A
    ARCAMONE, F
    NICOLELL.V
    PENCO, S
    OREZZI, P
    PIRELLI, A
    [J]. NATURE, 1964, 203 (494) : 1064 - +
  • [3] SYNTHESIS, DNA-BINDING PROPERTIES, AND ANTITUMOR-ACTIVITY OF NOVEL DISTAMYCIN DERIVATIVES
    ARCAMONE, FM
    ANIMATI, F
    BARBIERI, B
    CONFIGLIACCHI, E
    DALESSIO, R
    GERONI, C
    GIULIANI, FC
    LAZZARI, E
    MENOZZI, M
    MONGELLI, N
    PENCO, S
    VERINI, MA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (04) : 774 - 778
  • [4] Synthesis, in vitro antiproliferative activity, and DNA-binding properties of hybrid molecules containing pyrrolo[2,1-c][1,4]benzodiazepine and minor-groove-binding oligopyrrole carriers
    Baraldi, PG
    Balboni, G
    Cacciari, B
    Guiotto, A
    Manfredini, S
    Romagnoli, R
    Spalluto, G
    Thurston, DE
    Howard, PW
    Bianchi, N
    Rutigliano, C
    Mischiati, C
    Gambari, R
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (25) : 5131 - 5141
  • [5] Baraldi PG, 1999, ANTI-CANCER DRUG DES, V14, P71
  • [6] Baraldi PG, 2000, ARZNEIMITTEL-FORSCH, V50, P309
  • [7] Synthesis and antitumor activity of new benzoheterocyclic derivatives of distamycin A
    Baraldi, PG
    Romagnoli, R
    Beria, I
    Cozzi, P
    Geroni, C
    Mongelli, N
    Bianchi, N
    Mischiati, C
    Gambari, R
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (14) : 2675 - 2684
  • [8] Beran M, 1997, CLIN CANCER RES, V3, P2377
  • [9] ALTERATION OF THE EXPRESSION OF HUMAN ESTROGEN-RECEPTOR GENE BY DISTAMYCIN
    BIANCHI, N
    PASSADORE, M
    FERIOTTO, G
    MISCHIATI, C
    GAMBARI, R
    PIVA, R
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1995, 54 (5-6) : 211 - 215
  • [10] Targeting of the Sp1 binding sites of HIV-1 long terminal repeat with chromomycin - Disruption of nuclear factor center dot DNA complexes and inhibition of in vitro transcription
    Bianchi, N
    Passadore, M
    Rutigliano, C
    Feriotto, G
    Mischiati, C
    Gambari, R
    [J]. BIOCHEMICAL PHARMACOLOGY, 1996, 52 (10) : 1489 - 1498