Chronic Lymphocytic Leukemia Coverage from Every Angle

Tracking Clonal Evolution in Patients With Stable and Progressive CLL

By: Joseph Fanelli
Posted: Thursday, December 19, 2019

Findings from a longitudinal study presented in the Journal of Hematology & Oncology suggest that clonal evolution occurs in all patients with chronic lymphocytic leukemia (CLL), regardless of the clinical outcome of disease, although it occurs more quickly during disease progression. In particular, Rosa Visone, PhD, of the University G. d’Annunzio Chieti-Pescara, Italy, and colleagues reported that the frequency of nucleotide variants in specific CLL-related genes could indicate worse clinical outcomes.

“Our study points to higher genetic dynamics in [progressive CLL] and suggests that monitoring [variant allele frequency] of a specific gene panel in [peripheral blood mononuclear cells] from sequential samples of a CLL patient may predict disease progression,” the authors concluded.

In this study, the investigators enrolled a cohort of patients with CLL that included untreated sequential samples of progressive or stable disease. Genome-wide copy number variation analysis was used to investigate copy number fluctuations in 11 patients with stable disease and 15 patients with progressive disease. The investigators found that patients with progressive and stable CLL “seemed to have the same probability” of acquiring or losing clones but noted that this occurred more quickly in those with progressive disease.

Additionally, when exploring nucleotide variants with variant allele frequencies, the authors found on average 1.18 and 3.35 dynamic nucleotide variants per sample in stable and progressive CLL, respectively. Patients with progressive disease displayed higher gains and increases in dynamic nucleotide variants. Those patients with dynamic nucleotide variants greater than 1 had shorter treatment-free survival times and were associated with poor prognostic factors, including unmutated IgHV and trisomy 12.

Disclosure: The study authors reported no conflicts of interest.

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