Leukemia Research
Volume 29, Issue 2 , Pages 197-203, February 2005

The Notch ligand, Delta-1, alters retinoic acid (RA)-induced neutrophilic differentiation into monocytic and reduces RA-induced apoptosis in NB4 cells

  • Mai Murata-Ohsawa

      Affiliations

    • Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan
    • ,
  • Shuji Tohda

      Affiliations

    • Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 3 5803 5334; fax: +81 3 3818 1424.
    • ,
  • Hanae Kogoshi

      Affiliations

    • Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan
    • ,
  • Seiji Sakano

      Affiliations

    • Corporate R&D and Central Research Laboratory, Asahi Kasei Corporation, 2-1 Samejima, Fuji, Shizuoka 416-8501, Japan
    • ,
  • Nobuo Nara

      Affiliations

    • Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan

Received 16 February 2004; accepted 28 May 2004.

Abstract 

Effects of Notch activation on retinoic acid (RA)-induced differentiation and apoptosis were investigated. NB4, an acute promyelocytic leukemia (APL) cell line, undergoes neutrophilic differentiation and apoptosis by RA. Notch activation induced by a recombinant Notch ligand, Delta-1, did not affect the growth by itself. Treatment with RA plus Delta-1 made part of NB4 cells monocyte-like shaped and reduced the apoptosis. Similar phenomenon was also observed in primary APL cells. RA treatment induced cleavage of caspase-8 and PARP in NB4. Delta-1 suppressed the RA-induced cleavage of them, which may be a possible mechanism through which Delta-1 suppressed the RA-induced apoptosis.

Keywords: Notch, Delta, APL, Retinoic acid, Differentiation, PARP

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PII: S0145-2126(04)00238-3

doi:10.1016/j.leukres.2004.05.020

Leukemia Research
Volume 29, Issue 2 , Pages 197-203, February 2005

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