Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes
Abstract The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54571-w |
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| author | Qi Hu Yang Liu Qiuyu Yue Shuo Zhou Xianghong Jin Fan Lin Xiao-Jun Huang Junling Zhuang Jin Lu Xiaofei Gao Hsiang-Ying Lee |
| author_facet | Qi Hu Yang Liu Qiuyu Yue Shuo Zhou Xianghong Jin Fan Lin Xiao-Jun Huang Junling Zhuang Jin Lu Xiaofei Gao Hsiang-Ying Lee |
| author_sort | Qi Hu |
| collection | DOAJ |
| description | Abstract The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveils hyperactive CD8+ T cells and impaired erythropoiesis in the patient’s bone marrow. Unexpectedly, the patient’s erythroid cells display abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrate that lenalidomide treatment further augmented MHC-I expression in the patient’s erythroid cells. Blocking MHC-I or depleting T cells alleviates the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study implicates a mechanism underlying lenalidomide-induced PRCA in treating cancer patients. |
| format | Article |
| id | doaj-art-77d56fd9a7664ab886fdc1dcc472f68e |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-77d56fd9a7664ab886fdc1dcc472f68e2025-08-20T02:22:24ZengNature PortfolioNature Communications2041-17232024-11-0115111310.1038/s41467-024-54571-wLenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytesQi Hu0Yang Liu1Qiuyu Yue2Shuo Zhou3Xianghong Jin4Fan Lin5Xiao-Jun Huang6Junling Zhuang7Jin Lu8Xiaofei Gao9Hsiang-Ying Lee10Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic DiseaseMinistry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityMinistry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic DiseasePeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking UniversityDepartment of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic DiseaseKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake UniversityMinistry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityAbstract The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma. A multiple myeloma patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses reveal lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveils hyperactive CD8+ T cells and impaired erythropoiesis in the patient’s bone marrow. Unexpectedly, the patient’s erythroid cells display abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrate that lenalidomide treatment further augmented MHC-I expression in the patient’s erythroid cells. Blocking MHC-I or depleting T cells alleviates the defective erythropoiesis of PRCA, suggesting that the interaction between erythroid cells with elevated MHC-I and T cells in the bone marrow might contribute to PRCA. Taken together, our study implicates a mechanism underlying lenalidomide-induced PRCA in treating cancer patients.https://doi.org/10.1038/s41467-024-54571-w |
| spellingShingle | Qi Hu Yang Liu Qiuyu Yue Shuo Zhou Xianghong Jin Fan Lin Xiao-Jun Huang Junling Zhuang Jin Lu Xiaofei Gao Hsiang-Ying Lee Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes Nature Communications |
| title | Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes |
| title_full | Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes |
| title_fullStr | Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes |
| title_full_unstemmed | Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes |
| title_short | Lenalidomide-induced pure red cell aplasia is associated with elevated expression of MHC-I molecules on erythrocytes |
| title_sort | lenalidomide induced pure red cell aplasia is associated with elevated expression of mhc i molecules on erythrocytes |
| url | https://doi.org/10.1038/s41467-024-54571-w |
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