Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia: Beyond the Abstract

This study reports the strong impact of complex karyotype (CK) in chronic lymphocytic leukemia (CLL) after fludarabine related chemotherapy in addition to TP53 and IGHV mutational status.

Purine analogue triggers DNA lesions and oncogenic stress which in turn activate DNA repair pathways and apoptosis of leukemic cells. CK which reflects a genetic instability is probably the consequence of a defective DNA repair pathway. Consequently, when components of DNA repair signaling such as TP53, ATM (1-2) or ribosomal proteins 15 (RPS15) (3) are deteriorated; patients are more refractory to fludarabine-based therapeutical approaches. Conventional cytogenetic provides a pan-genomic information about instability and clonal architecture. This information is not available with FISH but requires the expertise of a cytogeneticist, which is not available in all centers.  SNP array is also interesting because it is a more sensitive approach to overcome the genomic instability and clonal diversity of progressive or fludarabine-refractory patients (4-5). More recent technological approaches such as next generation sequencing (6) and microarrayed single-cell sequencing (7) allow for better approach of the diversity of clonal architecture and the presence of subclones with strong prognostic impact with regard to clinical evolution and sensitivity to treatment. All these new techniques are not yet available daily but provide new possibilities for the future to identify high risk CLL patients. In the meantime, the identification of CK generates useful prognostic information.

Written by: LE BRIS Yannick

References: 
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