XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells

Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher che...

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Main Authors:	Moreno-Martínez, Daniel, Nomdedeu, Meritxell, Lara-Castillo, María Carmen, Etxabe, Amaia, Pratcorona, Marta, Tesi, Niccolò, Díaz-Beyá, Marina, Rozman, María, Montserrat, Emili, Urbano-Ispizua, Álvaro, Esteve, Jordi, Risueño, Ruth M.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147327/

id	pubmed-4147327
recordtype	oai_dc
spelling	pubmed-41473272014-08-29 XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells Moreno-Martínez, Daniel Nomdedeu, Meritxell Lara-Castillo, María Carmen Etxabe, Amaia Pratcorona, Marta Tesi, Niccolò Díaz-Beyá, Marina Rozman, María Montserrat, Emili Urbano-Ispizua, Álvaro Esteve, Jordi Risueño, Ruth M. Research Paper Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials. Impact Journals LLC 2014-05-26 /pmc/articles/PMC4147327/ /pubmed/24952669 Text en Copyright: © 2014 Moreno-Martínez et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Moreno-Martínez, Daniel Nomdedeu, Meritxell Lara-Castillo, María Carmen Etxabe, Amaia Pratcorona, Marta Tesi, Niccolò Díaz-Beyá, Marina Rozman, María Montserrat, Emili Urbano-Ispizua, Álvaro Esteve, Jordi Risueño, Ruth M.
spellingShingle	Moreno-Martínez, Daniel Nomdedeu, Meritxell Lara-Castillo, María Carmen Etxabe, Amaia Pratcorona, Marta Tesi, Niccolò Díaz-Beyá, Marina Rozman, María Montserrat, Emili Urbano-Ispizua, Álvaro Esteve, Jordi Risueño, Ruth M. XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
author_facet	Moreno-Martínez, Daniel Nomdedeu, Meritxell Lara-Castillo, María Carmen Etxabe, Amaia Pratcorona, Marta Tesi, Niccolò Díaz-Beyá, Marina Rozman, María Montserrat, Emili Urbano-Ispizua, Álvaro Esteve, Jordi Risueño, Ruth M.
author_sort	Moreno-Martínez, Daniel
title	XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
title_short	XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
title_full	XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
title_fullStr	XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
title_full_unstemmed	XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
title_sort	xiap inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells
description	Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.
publisher	Impact Journals LLC
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147327/
_version_	1613128570041794560

XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells

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