Cavallari Maurizio, Cavazzini Francesco, Bardi Antonella, Volta Eleonora, Melandri Aurora, Tammiso Elisa, Saccenti Elena, Lista Enrico, Quaglia Francesca Maria, Urso Antonio, Laudisi Michele, Menotti Elisa, Formigaro Luca, Dabusti Melissa, Ciccone Maria, Tomasi Paolo, Negrini Massimo, Cuneo Antonio, Rigolin Gian Matteo
Hematology Section, Department of Medical Sciences, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, University of Ferrara, Ferrara, Italy.
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Oncotarget. 2018 Sep 28;9(76):34398-34412. doi: 10.18632/oncotarget.26146.
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.
复杂核型（CK）在多种血液系统恶性肿瘤中是一种既定的不良预后标志物。在引入有效的促有丝分裂原后，越来越多的证据表明，通过传统染色体显带分析（CBA）检测到3种或更多畸变与慢性淋巴细胞白血病（CLL）的不良预后相关。因此，CBA的重要性得到了2018年CLL国际研讨会指南的认可，该指南提议在临床试验中引入CBA以验证核型畸变的价值。事实上，多项观察性研究表明，细胞遗传学畸变，尤其是CK，可能对接受化学免疫疗法治疗的患者以及可能接受基于新机制治疗的患者的客观预后指标（即首次治疗时间、无进展生存期、化疗难治时间和总生存期）产生负面独立影响。在此，我们着手阐述支持CK作为CLL预后标志物重要性的科学证据，并讨论表明CK是基因组不稳定结果的生物学基础。
