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Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia
Although mast cells (MC) play an important role in allergic reactions, their physiologic role remains unknown. In mice, several models of MC-deficiency have been developed. However, no comparable human model is available. We examined the in vitro- and in vivo effects of the KIT-targeting drug imatin...
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/PMC4413638/ https://www.ncbi.nlm.nih.gov/pubmed/25605011 |
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author | Cerny-Reiterer, Sabine Rabenhorst, Anja Stefanzl, Gabriele Herndlhofer, Susanne Hoermann, Gregor Müllauer, Leonhard Baumgartner, Sigrid Beham-Schmid, Christine Sperr, Wolfgang R Mannhalter, Christine Sill, Heinz Linkesch, Werner Arock, Michel Hartmann, Karin Valent, Peter |
author_facet | Cerny-Reiterer, Sabine Rabenhorst, Anja Stefanzl, Gabriele Herndlhofer, Susanne Hoermann, Gregor Müllauer, Leonhard Baumgartner, Sigrid Beham-Schmid, Christine Sperr, Wolfgang R Mannhalter, Christine Sill, Heinz Linkesch, Werner Arock, Michel Hartmann, Karin Valent, Peter |
author_sort | Cerny-Reiterer, Sabine |
collection | PubMed |
description | Although mast cells (MC) play an important role in allergic reactions, their physiologic role remains unknown. In mice, several models of MC-deficiency have been developed. However, no comparable human model is available. We examined the in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and development of human MC. Imatinib was found to inhibit stem cell factor (SCF)-induced differentiation of MC in long-term suspension cultures (IC50: 0.01 μM). Correspondingly, long-term treatment of chronic myeloid leukemia (CML) patients with imatinib (400 mg/day) resulted in a marked decrease in MC. In patients with continuous complete molecular response during therapy, bone marrow MC decreased to less than 5% of pre-treatment values, and also serum tryptase concentrations decreased significantly (pre-treatment: 32.0±11.1 ng/ml; post-therapy: 3.4±1.8, p<0.01). Other myeloid lineages, known to develop independently of KIT, were not affected by imatinib-therapy. Imatinib also produced a substantial decrease in MCdevelopment in mice. However, no clinical syndrome attributable to drug-induced MC-deficiency was recorded in our CML patients. Together, imatinib suppresses MC production in vitro and in vivo. However, drug-induced MC depletion is not accompanied by adverse clinical events, suggesting that MC are less relevant to homeostasis in healthy tissues than we assumed so far. |
format | Online Article Text |
id | pubmed-4413638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44136382015-05-08 Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia Cerny-Reiterer, Sabine Rabenhorst, Anja Stefanzl, Gabriele Herndlhofer, Susanne Hoermann, Gregor Müllauer, Leonhard Baumgartner, Sigrid Beham-Schmid, Christine Sperr, Wolfgang R Mannhalter, Christine Sill, Heinz Linkesch, Werner Arock, Michel Hartmann, Karin Valent, Peter Oncotarget Research Paper Although mast cells (MC) play an important role in allergic reactions, their physiologic role remains unknown. In mice, several models of MC-deficiency have been developed. However, no comparable human model is available. We examined the in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and development of human MC. Imatinib was found to inhibit stem cell factor (SCF)-induced differentiation of MC in long-term suspension cultures (IC50: 0.01 μM). Correspondingly, long-term treatment of chronic myeloid leukemia (CML) patients with imatinib (400 mg/day) resulted in a marked decrease in MC. In patients with continuous complete molecular response during therapy, bone marrow MC decreased to less than 5% of pre-treatment values, and also serum tryptase concentrations decreased significantly (pre-treatment: 32.0±11.1 ng/ml; post-therapy: 3.4±1.8, p<0.01). Other myeloid lineages, known to develop independently of KIT, were not affected by imatinib-therapy. Imatinib also produced a substantial decrease in MCdevelopment in mice. However, no clinical syndrome attributable to drug-induced MC-deficiency was recorded in our CML patients. Together, imatinib suppresses MC production in vitro and in vivo. However, drug-induced MC depletion is not accompanied by adverse clinical events, suggesting that MC are less relevant to homeostasis in healthy tissues than we assumed so far. Impact Journals LLC 2014-12-26 /pmc/articles/PMC4413638/ /pubmed/25605011 Text en Copyright: © 2015 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 | Research Paper Cerny-Reiterer, Sabine Rabenhorst, Anja Stefanzl, Gabriele Herndlhofer, Susanne Hoermann, Gregor Müllauer, Leonhard Baumgartner, Sigrid Beham-Schmid, Christine Sperr, Wolfgang R Mannhalter, Christine Sill, Heinz Linkesch, Werner Arock, Michel Hartmann, Karin Valent, Peter Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title | Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title_full | Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title_fullStr | Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title_full_unstemmed | Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title_short | Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia |
title_sort | long-term treatment with imatinib results in profound mast cell deficiency in ph+ chronic myeloid leukemia |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413638/ https://www.ncbi.nlm.nih.gov/pubmed/25605011 |
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