Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: A systematic reappraisal of classic cytogenetic data

Abstract

The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry 1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC ( 3 aberrations) was detected in 157 cases and significantly (P < 0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time-to-first-treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior.

Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference

“…7,14,15 Trisomy 12 is the second most frequent recurrent chromosomal aberration in CLL and is associated with clinical and biological heterogeneity, potentially linked to the presence of additional genomic aberrations. This concept is reinforced by our present findings regarding the biological background and clinical presentation/outcome of subgroups of +12 CLL patients defined by the presence of extra trisomies.…”

“…Panagiotis Baliakas, 1 Anna Puiggros, 2,3 Aliki Xochelli, 1,4 Lesley-Ann Sutton, 1 Florence Nguyen-Khac, 5 Anne Gardiner, 6 Karla Plevova, 7 Eva Minga, 4 Anastasia Hadzidimitriou,4 Renata Walewska, 6 Helen McCarthy, 6 Margarita Ortega, 8 Rosa Collado, 9 Teresa González, 10 Isabel Granada, 11 Elisa Luño, 12 Jana Kotašková, 7 Theodoros Moysiadis, 4 Zadie Davis, 6 Niki Stavroyianni, 13 Achilles Anagnostopoulos, 13 Jonathan C. Strefford, 14 Sarka Pospisilova, 7 Frederic Davi, 5 Anastasia Athanasiadou, 13 Richard Rosenquist, 1 David Oscier, 6 Blanca Espinet, 2,3 Figure 2. Kaplan-Meier curves for overall survival (OS).…”

In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI

“…A CK was observed in 41 of 287 of the cases (14.3%), a figure in keeping with data from recently published series of patients. 5 The CK was significantly associated with advanced Binet stage (P 5 .013), CD38 positivity (P 5 .003), b2-microglobulin concentration . 3.5 mg/L (P 5 .010), TP53 deletion or mutation (P 5 .001), higher CLL-IPI (P 5 .002), and intermediate unfavorable fluorescence in situ hybridization results (P , .001) (supplemental Table 4).…”

“…13 Furthermore, with the use of effective mitogens, cytogenetic abnormalities and, in particular, CK recently emerged as one of the novel biomarkers associated with an inferior outcome [4][5][6][7][8]12,20 and with the development of chemorefractoriness. 21 In conclusion, we showed for the first time that comorbidities and CK were associated with a worse outcome independently of CLL-IPI.…”

“…2 However, CLL is mainly a disease of the elderly with many patients presenting at diagnosis with significant comorbidities that may affect treatment decisions and outcome. 3 Moreover, in recent years, the complex karyotype (CK) emerged as a prognostic biomarker associated with an inferior outcome 4,5 and worse response to treatments including novel drugs. 6,7 We therefore set out to analyze the prognostic relevance of comorbidities and of CK in relation to the CLL-IPI.…”