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

Journal article


Ostasov, P., Robertson, H., Piazza, P., Datta, A., Apperley, J., Houdova, L., Lysak, D., Holubova, M., Tesarova, K., Caputo Galarce, V. and Barrozzi, I. (2020). Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report. Frontiers in Oncology. 10, p. 2356. https://doi.org/10.3389/fonc.2020.584607
AuthorsOstasov, P., Robertson, H., Piazza, P., Datta, A., Apperley, J., Houdova, L., Lysak, D., Holubova, M., Tesarova, K., Caputo Galarce, V. and Barrozzi, I.
Abstract

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.

Keywordsadvanced disease; case report; chronic lymphoid leukemia (CLL); disease progression; single-cell RNA-seq (scRNA-seq); therapy resistance
Year2020
JournalFrontiers in Oncology
Journal citation10, p. 2356
PublisherFrontiers Media
ISSN2234-943X
Digital Object Identifier (DOI)https://doi.org/10.3389/fonc.2020.584607
Publication dates
Online30 Oct 2020
Publication process dates
Accepted05 Oct 2020
Deposited17 Jun 2021
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Open
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