A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: Preliminary preclinical results

Danila Coradini, C. Pellizzaro, I. Scarlata, S. Zorzet, C. Garrovo, G. Abolafio, A. Speranza, M. Fedeli, S. Cantoni, G. Sava, M. G. Daidone, A. Perbellini

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish
Pages (from-to)785-792
Number of pages8
JournalLeukemia
Volume20
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Acute promyelocytic leukemia
  • Histone deacetylase inhibitor
  • Retinoic/butyric hyaluronan ester

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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