Přehled o publikaci
2024
Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single-cell RNA sequencing
KURUCOVÁ, Terézia; Kamila RÉBLOVÁ; Pavlína JANOVSKÁ; Jakub Paweł PORC; Veronika NAVRKALOVÁ et al.Basic information
Original name
Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single-cell RNA sequencing
Authors
KURUCOVÁ, Terézia; Kamila RÉBLOVÁ; Pavlína JANOVSKÁ; Jakub Paweł PORC; Veronika NAVRKALOVÁ; Šárka PAVLOVÁ; Jitka MALČÍKOVÁ; Karla PLEVOVÁ; Boris TICHÝ; Michael DOUBEK; Vítězslav BRYJA; Jana KOTAŠKOVÁ and Šárka POSPÍŠILOVÁ
Edition
MOLECULAR ONCOLOGY, ENGLAND, WILEY, 2024, 1574-7891
Other information
Language
English
Type of outcome
Article in a journal
Country of publisher
United States of America
Confidentiality degree
is not subject to a state or trade secret
References:
Marked to be transferred to RIV
Yes
RIV identification code
RIV/00216224:14110/24:00136116
Organization
Lékařská fakulta – Repository – Repository
UT WoS
EID Scopus
Keywords in English
CLL; clonal evolution; rare subpopulation; refractoriness; single-cell RNA sequencing
Links
GA23-05561S, research and development project. LX22NPO5102, research and development project. MUNI/A/1558/2023, interní kód Repo. NU20-08-00314, research and development project. NCMG III, large research infrastructures.
Changed: 10/6/2025 00:49, RNDr. Daniel Jakubík
Abstract
In the original language
Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single-cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (NOTCH1) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B-cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (CD19), membrane spanning 4-domains A1 (MS4A1; previously known as CD20), CD79a molecule (CD79A) and paired box 5 (PAX5), indicating B-cell de-differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single-cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time.
