Clonal evolution in chronic lymphocytic leukemia detected by fluorescence in situ hybridization and conventional cytogenetics after stimulation with CpG oligonucleotides and interleukin-2: a prospective analysis.
Chronic lymphocytic leukemia (CLL) patients may acquire new chromosome abnormalities during the course of their disease. Clonal evolution (CE) has been detected by conventional chromosome banding (CBA), several groups also confirmed CE with fluorescence in situ hybridization (FISH). At present, there are minimal prospective data on CE frequency determined using a combination of both methods. Therefore, the aim of our study was to prospectively assess CE frequency using a combination of FISH and CBA after stimulation with CpG oligonucleotides and interleukin-2. Between 2008 and 2012, we enrolled 140 patients with previously untreated CLL in a prospective trial evaluating CE using FISH and CBA after stimulation. Patients provided baseline and regular follow-up peripheral blood samples for testing. There was a median of 3 cytogenetic examinations (using both methods) per patient. CE was detected in 15.7% (22/140) of patients using FISH, in 28.6% (40/140) using CBA, and in 34.3% (48/140) of patients by combining both methods. Poor-prognosis CE (new deletion 17p, new deletion 11q or new complex karyotype) was detected in 15% (21/140) of patients and was significantly associated with previous CLL treatment (p=0.013). CBA provides more complex information about cytogenetic abnormalities in CLL patients than FISH and confirms that many patients can acquire new abnormalities during the course of their disease in a relatively short time period.
Department of Hematology, Hospital Novy Jicin, Czech Republic.
Martin
M
Brejcha
Laboratory of Medical Genetics - Department of Cytogenetics, AGEL Research and Training Institute - Novy Jicin Branch, AGEL Laboratories, Czech Republic.
Martina
M
Stoklasová
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Yvona
Y
Brychtová
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Anna
A
Panovská
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Kristina
K
Štěpanovská
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Gabriela
G
Vaňková
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Karla
K
Plevová
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Alexandra
A
Oltová
Laboratory of Medical Genetics - Department of Cytogenetics, AGEL Research and Training Institute - Novy Jicin Branch, AGEL Laboratories, Czech Republic.
Kateřina
K
Horká
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Šárka
Š
Pospíšilová
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Jiří
J
Mayer
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic. Electronic address: mdoubek@fnbrno.cz.
Michael
M
Doubek
D000328:Adult; D000368:Aged; D002871:Chromosome Banding; D060965:Clonal Evolution; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007376:Interleukin-2 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011446:Prospective Studies
C408982:CPG-oligonucleotide; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides
Chronic lymphocytic leukemia; Clonal evolution; CpG oligonucleotides; Cytogenetics; Fluorescence in situ hybridization; Interleukin-2