IgV_H gene mutation status and genomic imbalances in chronic lymphocytic leukaemia with increased prolymphocytes (CLL/PL)

Abstract

Chronic lymphocytic leukaemia (CLL) with increased prolymphocytes (CLL/PL) has been defined by the World Health Organization (WHO) classification and considered as a progressive and clinically aggressive variant of CLL. To further characterize the biological features of this disease, we performed IgVH gene mutational status, FISH and high-resolution comparative genomic hybridization (HR-CGH) analysis in 17 cases of CLL/PL. All CLL/PL utilized members of VH1, VH3 and VH4 families, with the highest prevalence of the VH1-69 gene. In all but one cases analyzed, the VH genes were unmutated. The FISH and HR-CGH analyses showed frequent occurrence of trisomy 12, del(11)(q23), del(17)(p13) and genetic imbalances, but recurrent genetic lesion characteristic for CLL/PL was not found. The follow-up HR-CGH analysis of two cases showed that increase of prolymphocytes in the course of CLL or CLL/PL are associated with clonal evolution and selection of the tumour clone. In conclusion, this study suggests that CLL/PL is a relatively homogeneous disease regarding VH gene mutation, but heterogeneous regarding genetic lesions. The heterogeneity and high number of genomic imbalances found in CLL/PL suggest that a genome-wide instability of the neoplastic cells may play a role in the development of the disease.

Population Pharmacogenomics and Personalized Medicine Research in Hungary: Achievements and Lessons Learned

“…This shift started a decade ago with the introduction of the HER-2 diagnostics of breast cancer. Pharmacogenomics has been subsequently applied, for example, in the context of acute lymphoblastic leukemia (ALL) [32,33], lung, breast and colorectal cancers, melanoma and oncology more generally [34][35][36][37][38][39][40][41][42][43][44][45][46]. Further research is however needed to discern the population genetic/genomic substructure of drug efficacy and safety in these therapeutic indications.…”