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The landscape of genetic mutations in patients with chronic lymphocytic leukaemia and complex karyotype

Stimulated conventional metaphase karyotype (CMK) is a reliable method to identify complex karyotype (CK), which has been associated with an unfavourable prognosis in patients with chronic lymphocytic leukaemia (CLL) (Thompson et al, 2015). Next generation sequencing (NGS) technology has advanced our knowledge of genomic aberrations occurring in CLL (Puente et al, 2011; Landau et al, 2015). While longitudinal studies demonstrated that mutated TP53 can associate with CK (Lazarian et al, 2016), overlap is not complete (Herling et al, 2016), and the genetic mutation landscape of patients with CLL and CK remains largely undescribed. A SureSelect custom panel of 295 genes (Agilent Technologies, Santa Clara, CA, USA) was applied to bone marrow aspirate samples collected between March 2003 and October 2015 (Data S1), as previously described (Takahashi et al, 2018). Stimulated CMK analysis was performed as previously described (Li et al, 2016). CK and high CK were defined as the presence of ≥3 and ≥5, clonal chromosome abnormalities, respectively, occurring in at least 2 out of 20 cells, either structural or numerical (Baliakas et al, 2019). Categorical variables were compared using the v or Fisher exact tests, continuous variables were compared using the Mann Whitney test, and logistic regression was used for multivariable analysis (MVA). To avoid the problem of multiplicity, we used the Benjamini and Hochberg method to correct adjusted P-values