Genetic Abnormalities in Chronic Lymphocytic Leukemia: Where We Are and Where We Go

Abstract

Chromosomal abnormalities in chronic lymphocytic leukemia (CLL) are detected in up to 80% of patients. Among them, deletions of 11q, 13q, 17p, and trisomy 12 have a known prognostic value and play an important role in CLL pathogenesis and evolution, determining patients outcome and therapeutic strategies. Standard methods used to identify these genomic aberrations include both conventional G-banding cytogenetics (CGC) and fluorescence in situ hybridization (FISH). Although FISH analyses have been implemented as the gold standard, CGC allows the identification of chromosomal translocations and complex karyotypes, the latest associated with poor outcome. Genomic arrays have a higher resolution that allows the detection of cryptic abnormalities, although these have not been fully implemented in routine laboratories. In the last years, next generation sequencing (NGS) methods have identified a wide range of gene mutations (e.g., TP53, NOTCH1, SF3B1, and BIRC3) which have improved our knowledge about CLL development, allowing us to refine both the prognostic subgroups and better therapeutic strategies. Clonal evolution has also recently arisen as a key point in CLL, integrating cytogenetic alterations and mutations in a dynamic model that improve our understanding about its clinical course and relapse.

Detection of Clonal Aberrations by Cytogenetic Analysis after Different Culture Methods and by FISH in 129 Patients with Chronic Lymphocytic Leukemia

“…Biallelic deletion of 13q14 was observed in 17% of the cases with both DNA probes D13S25 and D13S319, which is in the range reported previously [Garg et al, 2012]. The occurrence of trisomy 12, del (11) [Fabris et al, 2011;Ouilette et al, 2011;Véronèse et al, 2013;Xu et al, 2013;Puiggros et al, 2014;Stevens-Kroef et al, 2014]. However, these new assays share several limitations: the inability to detect balanced rearrangements, low-level mosaicism, and a clonal evolution of neoplastic B cells.…”

A network approach predicts NFKBIA and BIRC3 as pathogenic genes in childhood asthma

“…BIRC2/3-NIK signaling target effectors contribute directly to carcinogenesis (Yamato et al, 2015). It has been reported that chronic lymphocytic leukemia has BIRC3-associated abnormalities (Puiggros et al, 2014). Moreover, some researchers have suggested that Lynch syndrome and sporadic ovarian cancers differ by several deregulated genes such as BIRC3 (Jönsson et al, 2014).…”

Developing Hemophagocytic Syndrome during the transformation of Chronic Lymphocytic Leukemia: Case reports of t(7;14), t(14;19) and deletion of 17 p

“…Some genetical abnormalities are associated with bad prognosis. Especially, 11q, 13q, 17p deletions and trisomy 12 are important for prognosis (1,2). Firstly, 17p deletion was diagnosed in our patient using FISH method.…”