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

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.

Hematological malignancies

“… 18 It is diagnosed based on a blood smear and immunophenotyping by flow cytometry, although advanced studies have found that single-cell profiling of CLL at diagnosis can give the best treatment. 18 Among all cases, CLL was found to rank third, with a total of 25 cases, accounting for 11.9% of the total. This subtype was ranked the fifth in a study conducted between 1999-2013, where it constituted 8.6% of patients.…”

“…16 Chronic lymphoid leukemia (CLL) is reportedly most common in the western world, particularly among the elderly, and is characterized by increased lymphocytes in the bone marrow and blood. 18 It is diagnosed based on a blood smear and immunophenotyping by flow cytometry, although advanced studies have found that single-cell profiling of CLL at diagnosis can give the best treatment. 18 Among all cases, CLL was found to rank third, with a total of 25 cases, accounting for 11.9% of the total.…”

Investigação da infecção por Epstein Barr vírus (EBV) e associação com o perfil epidemiológico, clínico e citogenético de pacientes portadores de leucemia linfocítica crônica (LLC) / Investigation of Epstein Barr virus (EBV) infection and association with the epidemiological, clinical and cytogenetic profile of patients with chronic lymphocytic leukemia (LLC)

“…Um escore elevado de comorbidades influenciou negativamente na sobrevida relativa dos pacientes, mas sem efeito estatisticamente significativo na mortalidade (38) . Outro estudo semelhante, no entanto, identificou que pacientes idosos com disfunções renais possuíram mau prognóstico sob tratamento com fludarabina (39) .…”