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Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line
Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we p...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685516/ https://www.ncbi.nlm.nih.gov/pubmed/31428530 http://dx.doi.org/10.1080/2162402X.2019.1638210 |
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author | Kreutzman, Anna Yadav, Bhagwan Brummendorf, Tim H. Gjertsen, Bjorn Tore Hee Lee, Moon Janssen, Jeroen Kasanen, Tiina Koskenvesa, Perttu Lotfi, Kourosh Markevärn, Berit Olsson-Strömberg, Ulla Stentoft, Jesper Stenke, Leif Söderlund, Stina Udby, Lene Richter, Johan Hjorth-Hansen, Henrik Mustjoki, Satu |
author_facet | Kreutzman, Anna Yadav, Bhagwan Brummendorf, Tim H. Gjertsen, Bjorn Tore Hee Lee, Moon Janssen, Jeroen Kasanen, Tiina Koskenvesa, Perttu Lotfi, Kourosh Markevärn, Berit Olsson-Strömberg, Ulla Stentoft, Jesper Stenke, Leif Söderlund, Stina Udby, Lene Richter, Johan Hjorth-Hansen, Henrik Mustjoki, Satu |
author_sort | Kreutzman, Anna |
collection | PubMed |
description | Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naïve and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy. |
format | Online Article Text |
id | pubmed-6685516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-66855162019-08-19 Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line Kreutzman, Anna Yadav, Bhagwan Brummendorf, Tim H. Gjertsen, Bjorn Tore Hee Lee, Moon Janssen, Jeroen Kasanen, Tiina Koskenvesa, Perttu Lotfi, Kourosh Markevärn, Berit Olsson-Strömberg, Ulla Stentoft, Jesper Stenke, Leif Söderlund, Stina Udby, Lene Richter, Johan Hjorth-Hansen, Henrik Mustjoki, Satu Oncoimmunology Original Research Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naïve and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy. Taylor & Francis 2019-07-13 /pmc/articles/PMC6685516/ /pubmed/31428530 http://dx.doi.org/10.1080/2162402X.2019.1638210 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Kreutzman, Anna Yadav, Bhagwan Brummendorf, Tim H. Gjertsen, Bjorn Tore Hee Lee, Moon Janssen, Jeroen Kasanen, Tiina Koskenvesa, Perttu Lotfi, Kourosh Markevärn, Berit Olsson-Strömberg, Ulla Stentoft, Jesper Stenke, Leif Söderlund, Stina Udby, Lene Richter, Johan Hjorth-Hansen, Henrik Mustjoki, Satu Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title | Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title_full | Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title_fullStr | Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title_full_unstemmed | Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title_short | Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line |
title_sort | immunological monitoring of newly diagnosed cml patients treated with bosutinib or imatinib first-line |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685516/ https://www.ncbi.nlm.nih.gov/pubmed/31428530 http://dx.doi.org/10.1080/2162402X.2019.1638210 |
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