Lenalidomide-induced pure red cell aplasia: clinical characteristics and mechanistic analysis [bulkRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1021159 | ENA |
REPOSITORIES: ENA
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Project description:The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma, typically eliciting immune activation and myeloma cell clearance, alleviating anemia and associated symptoms. In a unique multiple myeloma case, the patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses revealed severe erythropoiesis impairment in this patient, with lenalidomide emerging as a pivotal disruptor of erythroid development, potentially driving PRCA. Single-cell transcriptome analysis unveiled a notable increase in hyperactive cluster of differentiation (CD)8+ T cells in the patient's bone marrow. The few remaining erythroid progenitors in the patient's bone marrow exhibited developmental dysfunction and immune-related pathway activation. Unexpectedly, these erythroid cells displayed abnormally high expression of major histocompatibility class I (MHCI). Functional assays demonstrated that the addition of lenalidomide further augmented MHCI expression in the patient's erythroid progenitors. Drug-induced increases in antigen presentation by immune erythrocytes emerged as the potential driving force behind hyperactive T cell attacks and subsequent development of PRCA. This study not only elucidates the mechanism underlying lenalidomide-induced PRCA in this rare case, but also underscore the importance of considering the MHCI gene in erythroid cells during clinical trials and drug administration.
2025-02-28 | GSE244043 | GEO
Project description:Lenalidomide-induced pure red cell aplasia: clinical characteristics and mechanistic analysis
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Project description:Lenalidomide-induced pure red cell aplasia: clinical characteristics and mechanistic analysis [scRNA-seq]
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Project description:The RVd therapy, combining lenalidomide, bortezomib, and dexamethasone, is a mainstay treatment for multiple myeloma, typically eliciting immune activation and myeloma cell clearance, alleviating anemia and associated symptoms. In a unique multiple myeloma case, the patient developed pure red cell aplasia (PRCA) following RVd treatment, despite the absence of common PRCA triggers. In vitro analyses revealed severe erythropoiesis impairment in this patient, with lenalidomide emerging as a pivotal disruptor of erythroid development, potentially driving PRCA. Single-cell transcriptome analysis unveiled a notable increase in hyperactive cluster of differentiation (CD)8+ T cells in the patient's bone marrow. The few remaining erythroid progenitors in the patient's bone marrow exhibited developmental dysfunction and immune-related pathway activation. Unexpectedly, these erythroid cells displayed abnormally high expression of major histocompatibility class I (MHCI). Functional assays demonstrated that the addition of lenalidomide further augmented MHCI expression in the patient's erythroid progenitors. Drug-induced increases in antigen presentation by immune erythrocytes emerged as the potential driving force behind hyperactive T cell attacks and subsequent development of PRCA. This study not only elucidates the mechanism underlying lenalidomide-induced PRCA in this rare case, but also underscore the importance of considering the MHCI gene in erythroid cells during clinical trials and drug administration.
2025-02-28 | GSE244044 | GEO
Project description: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 revealed lenalidomide as a pivotal disruptor of erythropoiesis. Single-cell transcriptome analysis unveiled hyperactive CD8+ T cells and impaired erythropoiesis in the patient's bone marrow. Unexpectedly, the patient's erythroid cells displayed abnormally high expression of genes in the antigen presentation pathway, particularly those for major histocompatibility class I (MHC-I) molecules. Functional assays demonstrated that lenalidomide treatment further augmented MHC-I expression in the patient's erythroid cells. Blocking MHC-I or depleting T cells alleviate 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 revealed a novel mechanism underlying lenalidomide-induced PRCA in treating cancer patients.
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Project description:Pure red cell aplasia (PRCA) is a rare disorder characterized by marked erythroid hypoplasia with maturation arrest in the bone marrow. Secondary acquired PRCA may be associated with hematologic disorders. A few case reports have described PRCA associated with multiple myeloma (MM). However, the clinical course and mechanism of PRCA associated with MM remain unknown. We herein report two cases of PRCA associated with MM in patients undergoing treatment with lenalidomide.
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Project description:Lenalidomide, an IMiD® immunomodulatory agent used for the treatment of multiple myeloma (MM),is believed to target the stromal support, but its precise mechanism on the phenotype or the effector functions of macrophages is still unclear. To investigate the effect of lenalidomide on macrophages, M-CSF generated macrophages were treated with Lenalidomide and analyzed by RNA-seq.
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