Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report

Frontiers in Oncology

Iros Barozzi¹  Jane Apperley²  Monika Holubova³  Daniel Lysak³  Pavel Ostasov⁴  Katerina Tesarova⁵  Valentina S. Caputo⁶  Paolo Piazza⁷  Avik Datta⁷  Henry Robertson⁷  Lucie Houdova⁹ 

[1] Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom;Department of Haematology and Oncology, University Hospital Pilsen, Pilsen, Czechia;Department of Surgery and Cancer, Imperial College London, London, United Kingdom;Faculty of Medicine in Pilsen, Institute of Medical Genetics, Charles University in Prague and Faculty Hospital, Pilsen, Czechia;;Hugh &Imperial BRC Genomics Facility, Imperial College London, London, United Kingdom;Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia;NTIS, Faculty of Applied Science, University of West Bohemia, Pilsen, Czechia;

关键词: chronic lymphoid leukemia (CLL);    single-cell RNA-seq (scRNA-seq);    therapy resistance;    disease progression;    advanced disease;    case report;   

DOI  :  10.3389/fonc.2020.584607

来源: DOAJ

【 摘 要 】

Genetic and transcriptional heterogeneity of Chronic lymphocytic leukaemia (CLL) limits prevention of disease progression. Longitudinal single-cell transcriptomics represents the state-of-the-art method to profile the disease heterogeneity at diagnosis and to inform about disease evolution. Here, we apply single-cell RNA-seq to a CLL case, sampled at diagnosis and relapse, that was treated with FCR (Fludarabine, Cyclophosphamide, Rituximab) and underwent a dramatic decrease in CD19 expression during disease progression. Computational analyses revealed a major switch in clones’ dominance during treatment. The clone that expanded at relapse showed 17p and 3p chromosomal deletions, and up-regulation of pathways related to motility, cytokine signaling and antigen presentation. Single-cell RNA-seq uniquely revealed that this clone was already present at low frequency at diagnosis, and it displays feature of plasma cell differentiation, consistent with a more aggressive phenotype. This study shows the benefit of single-cell profiling of CLL heterogeneity at diagnosis, to identify clones that might otherwise not be recognized and to determine the best treatment options.

【 授权许可】

Unknown