Compounds of the anthracycline family of antibiotics elevate human gamma-globin expression both in erythroid cultures and in a transgenic mouse model

Blood Cells, Molecules & Diseases
Pandelis SpyrouMarina Kleanthous

Abstract

We examined the effect of the anthracyclines aclarubicin, bleomycin, daunorubicin, doxorubicin and idarubicin on human gamma- and beta-globin promoter activity in an in vitro luciferase assay, ex vivo in erythroid cultures and in vivo in transgenic mice carrying the human gamma-globin gene. Effects in erythroid liquid cultures derived from healthy donors were assayed by evaluating HbF production with high performance liquid chromatography and by measuring mRNA levels of the globin genes and the proportion of erythroblasts containing HbF. Compounds testing positive in the in vitro and ex vivo assays were applied to erythroid cultures derived from thalassaemic patients. Doxorubicin, idarubicin and daunorubicin increased HbF production in cultures of both, healthy and thalassaemic donors. Daunorubicin induced HbF in thalassaemic cells ex vivo with the highest statistical significance and, importantly and in contrast to the clinical HbF inducer hydroxyurea, showed specific induction of gamma-globin without associated induction of alpha-globin. Daunorubicin was screened in transgenic mice carrying the human (A)gamma-globin gene, and it resulted in increased (A)gamma-globin mRNA levels. Our results indicate that anthracyclines are a ...Continue Reading

References

Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T EnverG Stamatoyannopoulos
Apr 8, 2003·Current Medicinal Chemistry·Marek GniazdowskiMalgorzata Czyz
Sep 28, 2005·Biochemical Pharmacology·Malgorzata CzyzMarkus Düchler
Jan 23, 2008·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M SerenoM González-Barón

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Citations

Dec 16, 2010·Current Opinion in Pediatrics·Daniel E Bauer, Stuart H Orkin
Aug 12, 2014·Nucleosides, Nucleotides & Nucleic Acids·Ping ZhaoQian-Yun Bin

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