title: IgVH 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.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Balogh
authors.forename: Lilla
authors.initials: L
authors.lastname: Reiniger
authors.forename: Linda
authors.initials: L
authors.lastname: Deák
authors.forename: Csaba
authors.initials: C
authors.lastname: Bödör
authors.forename: Judit
authors.initials: J
authors.lastname: Csomor
authors.forename: Agota
authors.initials: A
authors.lastname: Szepesi
authors.forename: Eva
authors.initials: E
authors.lastname: Gagyi
authors.forename: László
authors.initials: L
authors.lastname: Kopper
authors.forename: András
authors.initials: A
authors.lastname: Matolcsy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region