Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia

Abstract

The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations. Indeed, a number of observational studies showed that cytogenetic aberrations and, particularly, the CK may have a negative independent impact on objective outcome measures (i.e. time to first treatment, progression free survival, time to chemorefractoriness and overall survival) both in patients treated with chemoimmunotherapy and, possibly, in patients receiving novel mechanism-based treatment. Here, we set out to present the scientific evidence supporting the significance of CK as a prognostic marker in CLL and to discuss the biological basis showing that the CK is a consequence of genomic instability.

Keywords: Richter transformation; chronic lymphocytic leukemia; complex karyotype; prognosis; target therapy.

Figure 1

(A) Frequency of Gene Mutation by NGS in patient with or without CK reported by Rigolin et al [26] (B) Frequency of Gene Mutation by NGS in patient with or without CK reported by Herling et al [24]. ^*p<0.05

Figure 2. Genetic background favouring the development of complex karyotype

Figure 3

Frequency of TP53 disruption (A), ATM deletion (B), and unmutated IGHV gene configuration (C) according to the presence or absence of CK. The number of cases are reported aside each bar. NS: not significant; UM-IGHV: unmutated IGHV.