TY - JOUR
T1 - A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia
T2 - Preliminary preclinical results
AU - Coradini, Danila
AU - Pellizzaro, C.
AU - Scarlata, I.
AU - Zorzet, S.
AU - Garrovo, C.
AU - Abolafio, G.
AU - Speranza, A.
AU - Fedeli, M.
AU - Cantoni, S.
AU - Sava, G.
AU - Daidone, M. G.
AU - Perbellini, A.
PY - 2006/5
Y1 - 2006/5
N2 - All-trans retinoic acid (ATRA) represents the therapy of choice for patients with acute promyelocytic leukemia (APL). However, patients often relapse due to ATRA-resistance. The molecular basis of APL alterations indicates that addition of a histone deacetylase inhibitor to ATRA may restore the sensitivity to retinoids. We explored the in vitro and in vivo effects of a novel retinoic/butyric hyaluronan ester (HBR) on a retinoic acid (RA)-sensitive human myeloid cell line, NB4, and on its RA-resistant subclone, NB4.007/6. In vitro, HBR induced growth arrest and terminal differentiation in RA-sensitive NB4 cells (as confirmed by an increased expression of CD11 family members and nitroblue tetrazolium assay), whereas it inhibited the growth of RA-resistant cells by apoptosis, paralleled by an increase in the levels of caspase 3 and 7. In vivo, HBR treatment of NB4-inoculated severe combined immunodeficient mice resulted in a statistically significant increase in survival time (P
AB - All-trans retinoic acid (ATRA) represents the therapy of choice for patients with acute promyelocytic leukemia (APL). However, patients often relapse due to ATRA-resistance. The molecular basis of APL alterations indicates that addition of a histone deacetylase inhibitor to ATRA may restore the sensitivity to retinoids. We explored the in vitro and in vivo effects of a novel retinoic/butyric hyaluronan ester (HBR) on a retinoic acid (RA)-sensitive human myeloid cell line, NB4, and on its RA-resistant subclone, NB4.007/6. In vitro, HBR induced growth arrest and terminal differentiation in RA-sensitive NB4 cells (as confirmed by an increased expression of CD11 family members and nitroblue tetrazolium assay), whereas it inhibited the growth of RA-resistant cells by apoptosis, paralleled by an increase in the levels of caspase 3 and 7. In vivo, HBR treatment of NB4-inoculated severe combined immunodeficient mice resulted in a statistically significant increase in survival time (P
KW - Acute promyelocytic leukemia
KW - Histone deacetylase inhibitor
KW - Retinoic/butyric hyaluronan ester
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UR - http://www.scopus.com/inward/citedby.url?scp=33646122237&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2404179
DO - 10.1038/sj.leu.2404179
M3 - Article
C2 - 16525489
AN - SCOPUS:33646122237
VL - 20
SP - 785
EP - 792
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 5
ER -