Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: A new approach to anti-leukemia therapy

H. Kosugi, M. Towatari, S. Hatano, K. Kitamura, H. Kiyoi, T. Kinoshita, M. Tanimoto, T. Murate, K. Kawashima, H. Saito, T. Naoe

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Abstract

We investigated the effect of the histone deacetylase inhibitors (HDIs), trichostatin A and trapoxin A on leukemia cells and cell lines from the viewpoint of differentiation induction. TSA induced differentiation in erythroid cell lines by itself, whereas it synergistically enhanced the differentiation that was directed by all-trans retinoic acid (ATRA) or vitamin D3 in U937, HL60 and NB4 cells. The combined treatment of HDI with ATRA induced differentiation in ATRA-resistant HL60 and NB4 cells. The transcriptional expression during the treatment with HDI was examined in HL60, U937 and MEG-01. Cell cycle-regulator genes (p21(waf1) and p16(INK4A)) were upregulated or constantly expressed, erythroid-specific genes (GATA-1, β-globin) were silent or downregulated, and housekeeping genes (β-actin and GAPDH) were constantly expressed. Twelve of 35 (34%) clinical samples from AML patients ranging from M0 to M7 also displayed both phenotypical and morphological changes by the treatment with TSA alone. HDIs are thus the potent inducer or enhancer of differentiation in acute myeloid leukemia and regulate transcription in an ordered manner.

Original languageEnglish
Pages (from-to)1316-1324
Number of pages9
JournalLeukemia
Volume13
Issue number9
DOIs
Publication statusPublished - Jan 1 1999

Keywords

  • Differentiation
  • Histone deacetylase inhibitor
  • Leukemia
  • Trapoxin A
  • Trichostatin A

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Kosugi, H., Towatari, M., Hatano, S., Kitamura, K., Kiyoi, H., Kinoshita, T., Tanimoto, M., Murate, T., Kawashima, K., Saito, H., & Naoe, T. (1999). Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: A new approach to anti-leukemia therapy. Leukemia, 13(9), 1316-1324. https://doi.org/10.1038/sj.leu.2401508