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

Maurizio Cavallari, Francesco Cavazzini, Antonella Bardi, Eleonora Volta, Aurora Melandri, Elisa Tammiso, Elena Saccenti, Enrico Lista, Francesca Maria Quaglia, Antonio Urso, Michele Laudisi, Elisa Menotti, Luca Formigaro, Melissa Dabusti, Maria Ciccone, Paolo Tomasi, Massimo Negrini, Antonio Cuneo _ and Gian Matteo Rigolin

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Oncotarget. 2018; 9:34398-34412. https://doi.org/10.18632/oncotarget.26146

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Abstract

Maurizio Cavallari1,*, Francesco Cavazzini1,*, Antonella Bardi1, Eleonora Volta1, Aurora Melandri1, Elisa Tammiso1, Elena Saccenti1, Enrico Lista1, Francesca Maria Quaglia1, Antonio Urso1, Michele Laudisi1, Elisa Menotti1, Luca Formigaro1, Melissa Dabusti1, Maria Ciccone1, Paolo Tomasi1, Massimo Negrini2, Antonio Cuneo1,* and Gian Matteo Rigolin1,*

1Hematology Section, Department of Medical Sciences, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, University of Ferrara, Ferrara, Italy

2Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

*These authors have contributed equally to this work

Correspondence to:

Antonio Cuneo, email: [email protected]

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

Received: April 05, 2018     Accepted: September 01, 2018     Published: September 28, 2018

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.


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