miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape
Abstract We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56383-y |
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| author | Fang Chen Dandan Zhao Yongfang Xu Yi Zhang Min-Hsuan Chen Khyatiben V. Pathak Nate Hansen Brooke Lovell Yong Liang Katrina Estrella Wei-Le Wang Lucy Ghoda Russell Rockne Xiwei Wu Haris Ali Jianhua Yu Michael A. Caligiuri Stephen J. Forman Jeff M. Trent Ya-Huei Kuo Ling Li Piotr Swiderski Jianying Zhang Marcin Kortylewski Le Xuan Truong Nguyen Patrick Pirrotte Mark Boldin Guido Marcucci Bin Zhang |
| author_facet | Fang Chen Dandan Zhao Yongfang Xu Yi Zhang Min-Hsuan Chen Khyatiben V. Pathak Nate Hansen Brooke Lovell Yong Liang Katrina Estrella Wei-Le Wang Lucy Ghoda Russell Rockne Xiwei Wu Haris Ali Jianhua Yu Michael A. Caligiuri Stephen J. Forman Jeff M. Trent Ya-Huei Kuo Ling Li Piotr Swiderski Jianying Zhang Marcin Kortylewski Le Xuan Truong Nguyen Patrick Pirrotte Mark Boldin Guido Marcucci Bin Zhang |
| author_sort | Fang Chen |
| collection | DOAJ |
| description | Abstract We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells’ metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies. |
| format | Article |
| id | doaj-art-5d4530d178eb464bb6726e3cac6b84e1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5d4530d178eb464bb6726e3cac6b84e12025-02-02T12:32:24ZengNature PortfolioNature Communications2041-17232025-02-0116112110.1038/s41467-025-56383-ymiR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escapeFang Chen0Dandan Zhao1Yongfang Xu2Yi Zhang3Min-Hsuan Chen4Khyatiben V. Pathak5Nate Hansen6Brooke Lovell7Yong Liang8Katrina Estrella9Wei-Le Wang10Lucy Ghoda11Russell Rockne12Xiwei Wu13Haris Ali14Jianhua Yu15Michael A. Caligiuri16Stephen J. Forman17Jeff M. Trent18Ya-Huei Kuo19Ling Li20Piotr Swiderski21Jianying Zhang22Marcin Kortylewski23Le Xuan Truong Nguyen24Patrick Pirrotte25Mark Boldin26Guido Marcucci27Bin Zhang28Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteIntegrative Genomics Core, City of Hope Beckman Research InstituteCancer & Cell Biology Division, Translational Genomics Research InstituteCancer & Cell Biology Division, Translational Genomics Research InstituteCancer & Cell Biology Division, Translational Genomics Research InstituteDNA/RNA Peptide Shared Resources, City of Hope Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Systems Biology, City of Hope Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Computational and Quantitative Medicine, City of Hope Beckman Research InstituteIntegrative Genomics Core, City of Hope Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical CenterDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical CenterDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical CenterCancer & Cell Biology Division, Translational Genomics Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDNA/RNA Peptide Shared Resources, City of Hope Beckman Research InstituteDepartment of Computational and Quantitative Medicine, City of Hope Beckman Research InstituteDepartment of Immuno-Oncology, City of Hope Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteCancer & Cell Biology Division, Translational Genomics Research InstituteDepartment of Systems Biology, City of Hope Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research InstituteAbstract We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells’ metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies.https://doi.org/10.1038/s41467-025-56383-y |
| spellingShingle | Fang Chen Dandan Zhao Yongfang Xu Yi Zhang Min-Hsuan Chen Khyatiben V. Pathak Nate Hansen Brooke Lovell Yong Liang Katrina Estrella Wei-Le Wang Lucy Ghoda Russell Rockne Xiwei Wu Haris Ali Jianhua Yu Michael A. Caligiuri Stephen J. Forman Jeff M. Trent Ya-Huei Kuo Ling Li Piotr Swiderski Jianying Zhang Marcin Kortylewski Le Xuan Truong Nguyen Patrick Pirrotte Mark Boldin Guido Marcucci Bin Zhang miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape Nature Communications |
| title | miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape |
| title_full | miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape |
| title_fullStr | miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape |
| title_full_unstemmed | miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape |
| title_short | miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape |
| title_sort | mir 142 deficit in t cells during blast crisis promotes chronic myeloid leukemia immune escape |
| url | https://doi.org/10.1038/s41467-025-56383-y |
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