TY - JOUR
T1 - Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia
T2 - A new approach to anti-leukemia therapy
AU - Kosugi, H.
AU - Towatari, M.
AU - Hatano, S.
AU - Kitamura, K.
AU - Kiyoi, H.
AU - Kinoshita, T.
AU - Tanimoto, M.
AU - Murate, T.
AU - Kawashima, K.
AU - Saito, H.
AU - Naoe, T.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Differentiation
KW - Histone deacetylase inhibitor
KW - Leukemia
KW - Trapoxin A
KW - Trichostatin A
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UR - http://www.scopus.com/inward/citedby.url?scp=0032879920&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2401508
DO - 10.1038/sj.leu.2401508
M3 - Article
C2 - 10482980
AN - SCOPUS:0032879920
SN - 0887-6924
VL - 13
SP - 1316
EP - 1324
JO - Leukemia
JF - Leukemia
IS - 9
ER -
