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Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia

The treatment of chronic myeloid leukemia (CML), a disease caused by t(9;22)(q34;q11) reciprocal translocation, has advanced largely through the use of targeted tyrosine kinase inhibitors (TKIs). To identify molecular differences that might distinguish TKI responders from non-responders, we performe...

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Autores principales: Zhang, Weilong, Yang, Beibei, Weng, Linqian, Li, Jiangtao, Bai, Jiefei, Wang, Ting, Wang, Jingwen, Ye, Jin, Jing, Hongmei, Jiao, Yuchen, Chen, Xixi, Liu, Hui, Zeng, Yi-Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803567/
https://www.ncbi.nlm.nih.gov/pubmed/33226961
http://dx.doi.org/10.18632/aging.104136
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author Zhang, Weilong
Yang, Beibei
Weng, Linqian
Li, Jiangtao
Bai, Jiefei
Wang, Ting
Wang, Jingwen
Ye, Jin
Jing, Hongmei
Jiao, Yuchen
Chen, Xixi
Liu, Hui
Zeng, Yi-Xin
author_facet Zhang, Weilong
Yang, Beibei
Weng, Linqian
Li, Jiangtao
Bai, Jiefei
Wang, Ting
Wang, Jingwen
Ye, Jin
Jing, Hongmei
Jiao, Yuchen
Chen, Xixi
Liu, Hui
Zeng, Yi-Xin
author_sort Zhang, Weilong
collection PubMed
description The treatment of chronic myeloid leukemia (CML), a disease caused by t(9;22)(q34;q11) reciprocal translocation, has advanced largely through the use of targeted tyrosine kinase inhibitors (TKIs). To identify molecular differences that might distinguish TKI responders from non-responders, we performed single cell RNA sequencing on cells (n = 41,723 cells) obtained from the peripheral blood of four CML patients at different stages of treatment to generate single cell expression profiles. Analysis of our single cell expression profiles in conjunction with those previously obtained from the bone marrow of additional CML patients and healthy donors (total = 69,263 cells) demonstrated that imatinib treatment significantly altered leukocyte population compositions in both responders and non-responders, and affected the expression profiles of multiple cell populations, including non-neoplastic cell types. Notably, in imatinib poor-responders, patient-specific pre-treatment unique stem/progenitor cells became enriched in peripheral blood compared to the responders. These results indicate that resistance to TKIs might be intrinsic in some CML patients rather than acquired, and that non-neoplastic immune cell types may also play vital roles in dispersing the responsiveness of patients to TKIs. Furthermore, these results demonstrated the potential utility of peripheral blood as a diagnostic tool in the TKI sensitivity of CML patients.
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spelling pubmed-78035672021-01-15 Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia Zhang, Weilong Yang, Beibei Weng, Linqian Li, Jiangtao Bai, Jiefei Wang, Ting Wang, Jingwen Ye, Jin Jing, Hongmei Jiao, Yuchen Chen, Xixi Liu, Hui Zeng, Yi-Xin Aging (Albany NY) Research Paper The treatment of chronic myeloid leukemia (CML), a disease caused by t(9;22)(q34;q11) reciprocal translocation, has advanced largely through the use of targeted tyrosine kinase inhibitors (TKIs). To identify molecular differences that might distinguish TKI responders from non-responders, we performed single cell RNA sequencing on cells (n = 41,723 cells) obtained from the peripheral blood of four CML patients at different stages of treatment to generate single cell expression profiles. Analysis of our single cell expression profiles in conjunction with those previously obtained from the bone marrow of additional CML patients and healthy donors (total = 69,263 cells) demonstrated that imatinib treatment significantly altered leukocyte population compositions in both responders and non-responders, and affected the expression profiles of multiple cell populations, including non-neoplastic cell types. Notably, in imatinib poor-responders, patient-specific pre-treatment unique stem/progenitor cells became enriched in peripheral blood compared to the responders. These results indicate that resistance to TKIs might be intrinsic in some CML patients rather than acquired, and that non-neoplastic immune cell types may also play vital roles in dispersing the responsiveness of patients to TKIs. Furthermore, these results demonstrated the potential utility of peripheral blood as a diagnostic tool in the TKI sensitivity of CML patients. Impact Journals 2020-11-23 /pmc/articles/PMC7803567/ /pubmed/33226961 http://dx.doi.org/10.18632/aging.104136 Text en Copyright: © 2020 Zhang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Weilong
Yang, Beibei
Weng, Linqian
Li, Jiangtao
Bai, Jiefei
Wang, Ting
Wang, Jingwen
Ye, Jin
Jing, Hongmei
Jiao, Yuchen
Chen, Xixi
Liu, Hui
Zeng, Yi-Xin
Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title_full Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title_fullStr Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title_full_unstemmed Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title_short Single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
title_sort single cell sequencing reveals cell populations that predict primary resistance to imatinib in chronic myeloid leukemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803567/
https://www.ncbi.nlm.nih.gov/pubmed/33226961
http://dx.doi.org/10.18632/aging.104136
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