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Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia
Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph(+) chronic myeloid leukemia. We here report that primary cells and cell lines derived from pat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012724/ https://www.ncbi.nlm.nih.gov/pubmed/24681707 |
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author | Cerny-Reiterer, Sabine Meyer, Renata A. Herrmann, Harald Peter, Barbara Gleixner, Karoline V. Stefanzl, Gabriele Hadzijusufovic, Emir Pickl, Winfried F. Sperr, Wolfgang R. Melo, Junia V. Maeda, Hiroshi Jäger, Ulrich Valent, Peter |
author_facet | Cerny-Reiterer, Sabine Meyer, Renata A. Herrmann, Harald Peter, Barbara Gleixner, Karoline V. Stefanzl, Gabriele Hadzijusufovic, Emir Pickl, Winfried F. Sperr, Wolfgang R. Melo, Junia V. Maeda, Hiroshi Jäger, Ulrich Valent, Peter |
author_sort | Cerny-Reiterer, Sabine |
collection | PubMed |
description | Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph(+) chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. Highly enriched CD34(+)/CD38(−) ALL stem cells also expressed Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and growth arrest in the BCR/ABL1(+) cell lines, in Ph(−) lymphoblastic cell lines and in primary Ph(+) and Ph(−) ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of leukemic cells were dose-dependent. In Ph(+) ALL, major growth-inhibitory effects of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib-resistant cells. Hsp32-targeting drugs were found to synergize with imatinib, nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph(+) ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL cells and to synergize with imatinib in suppressing the growth of ALL cells. In conclusion, Hsp32 is an essential survival factor and potential new target in ALL. |
format | Online Article Text |
id | pubmed-4012724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-40127242014-05-09 Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia Cerny-Reiterer, Sabine Meyer, Renata A. Herrmann, Harald Peter, Barbara Gleixner, Karoline V. Stefanzl, Gabriele Hadzijusufovic, Emir Pickl, Winfried F. Sperr, Wolfgang R. Melo, Junia V. Maeda, Hiroshi Jäger, Ulrich Valent, Peter Oncotarget Priority Research Paper Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph(+) chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. Highly enriched CD34(+)/CD38(−) ALL stem cells also expressed Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and growth arrest in the BCR/ABL1(+) cell lines, in Ph(−) lymphoblastic cell lines and in primary Ph(+) and Ph(−) ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of leukemic cells were dose-dependent. In Ph(+) ALL, major growth-inhibitory effects of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib-resistant cells. Hsp32-targeting drugs were found to synergize with imatinib, nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph(+) ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL cells and to synergize with imatinib in suppressing the growth of ALL cells. In conclusion, Hsp32 is an essential survival factor and potential new target in ALL. Impact Journals LLC 2014-03-04 /pmc/articles/PMC4012724/ /pubmed/24681707 Text en Copyright: © 2014 Cerny-Reiterer 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. |
spellingShingle | Priority Research Paper Cerny-Reiterer, Sabine Meyer, Renata A. Herrmann, Harald Peter, Barbara Gleixner, Karoline V. Stefanzl, Gabriele Hadzijusufovic, Emir Pickl, Winfried F. Sperr, Wolfgang R. Melo, Junia V. Maeda, Hiroshi Jäger, Ulrich Valent, Peter Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title | Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title_full | Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title_fullStr | Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title_full_unstemmed | Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title_short | Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia |
title_sort | identification of heat shock protein 32 (hsp32) as a novel target in acute lymphoblastic leukemia |
topic | Priority Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012724/ https://www.ncbi.nlm.nih.gov/pubmed/24681707 |
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