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Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide and interleukin‐2 stimulation: A Belgian multicentric study
Author(s) -
Put Natalie,
Konings Peter,
Rack Katrina,
Jamar Mauricette,
Roy Nadine Van,
Libouton JeanneMarie,
Vannuffel Pascal,
Sartenaer Daniel,
Ameye Geneviève,
Speleman Frank,
Herens Christian,
Poirel Hélène A.,
Moreau Yves,
Hagemeijer Anne,
Vandenberghe Peter,
Michaux Lucienne
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20691
Subject(s) - cytogenetics , karyotype , clone (java method) , bone marrow , chronic lymphocytic leukemia , microbiology and biotechnology , cpg site , biology , leukemia , pathology , medicine , immunology , chromosome , genetics , gene , dna methylation , gene expression
We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis ( n = 172) or during disease evolution ( n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B‐cell mitogen 12‐ O ‐tetradecanoyl‐phorbol‐13‐acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin‐2 (IL‐2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL‐2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL‐2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL‐2 and 38% with TPA ( P < 0.0001). Application of FISH ( n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) ( n = 71), del(11q) ( n = 5), +12 ( n = 2), del(14q) ( n = 1), and del(17p) ( n = 1). In conclusion, our results confirm that CpG/IL‐2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques. © 2009 Wiley‐Liss, Inc.