Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis.
Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.e. 13q-single or normal), group 2 (intermediate risk, i.e. +12, 6q-, 1-2 anomalies), group 3 (unfavourable, i.e. 17p-, 11q-, complex karyotype), or group 4 (14q32/IGH translocation). Endpoints were treatment-free survival (TFS) and overall survival (OS). One hundred and ten patients were included in group 1, 99 in group 2, 25 in group 3 and 18 in group 4. 14q32/IGH translocation partners were identified in eight cases (BCL2 in five cases, BCL11A, CCND3 and CDK6 in one case each). group 4 showed shorter TFS versus groups 2 and 1 (25% patients treated at 2 months vs. 12 (P = 0.02) and 20 months (P = 0.002), respectively) and shorter OS (25% patients dead at 18 months versus 50 (P = 0.0003) and >60 months (P < 0.0001) respectively. The 14q32/IGH translocation maintained prognostic significance at multivariate analysis on TFS (P = 0.025) and OS (P < 0.001), along with advanced stage and CD38+. These findings show that the 14q32/IGH translocation predicts for an unfavourable outcome in CLL and that this cytogenetic subset might be included as a separate entity in a hierarchical cytogenetic classification of CLL.
Section of Haematology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy.
Francesco
F
Cavazzini
Jose Angel
JA
Hernandez
Alessandro
A
Gozzetti
Antonella
A
Russo Rossi
Cristiano
C
De Angeli
Ruana
R
Tiseo
Antonella
A
Bardi
Elisa
E
Tammiso
Rosaria
R
Crupi
Maria Pia
MP
Lenoci
Francesco
F
Forconi
Francesco
F
Lauria
Roberto
R
Marasca
Rossana
R
Maffei
Giuseppe
G
Torelli
Marcos
M
Gonzalez
Patricia
P
Martin-Jimenez
Jesus
J
Maria Hernandez
Gian Matteo
GM
Rigolin
Antonio
A
Cuneo
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051997:ADP-ribosyl Cyclase 1