The prognostic significance of genomic complexity in patients with CLL

Abstract

Chromosomal aberrations are a common feature of cancer and can fuel cancer progression and treatment resistance. In chronic lymphocytic leukemia (CLL), the presence of multiple chromosomal aberrations is commonly referred to as “genomic complexity” or “complex karyotype”– (CKT). In the context of chemo- and chemoimmunotherapy, genomic complexity is associated with poor response to treatment and short survival, while some targeted therapies are able to mitigate its adverse prognostic impact. This article reviews currently available data and literature on the role of genomic complexity in CLL. The currently established tools to measure genomic complexity in patients with CLL are summarized and their strengths and weaknesses for routine diagnostics are evaluated. Moreover, possible definitions of CKT as an indicator for genomic complexity are discussed. Finally, data on the impact of CKT on clinical outcomes of patients with CLL are reviewed and the implications for patient stratification are presented.

Keywords:

• CLL
• complex karyotype
• genomic instability
• prognosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

EG reports honoraria from AbbVie and AstraZeneca; travel grants from AbbVie. OAS reports personal fees and honoraria from AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Genmab, Gilead, Janssen, Eli Lilly, Roche; research funding from AbbVie, BeiGene, Janssen, Roche.

Additional information

Funding

The OAS received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project number 524342988.