TP53 gene aberrations (mutation and/or deletion 17p) are the most important adverse prognostic and predictive markers in CLL • Low-burden TP53 mutations are often detectable in CLL cells prior to the therapy and expand upon the selective pressure of chemoimmunotherapy • Other genomic alterations accompany aberrations in the TP53 gene • Bulk analysis (such as whole genome/exome sequencing or genomic array) cannot precisely determine the co-occurrence of abnormalities in individual cells • Expression profiles of cells bearing TP53 mutation are altered and may be distinguished from expression profiles of unaffected cells using single-cell RNA sequencing (scRNA-seq). We aimed to explore the possibility to identify and characterize populations of CLL cells resistant to treatment and causing refractoriness in samples from patients with disease relapse. We tried to trace back the refractory cells in samples prior to the therapy using scRNA-seq in patients with TP53 mutations