Good prognosis cytogenetics in B-cell chronic lymphocytic leukemia is associated in vitro with low susceptibility to apoptosis and enhanced immunogenicity.
Chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) have been shown to correlate with prognosis. Little is known about the relationship between chromosomal abnormalities and biological behavior of B-CLL cells in vitro. The present study was designed to explore the impact of chromosomal abnormalities determined by interphase fluorescence in situ hybridization (FISH) on the in vitro survival and immunogenicity of B-CLL. Considerable heterogeneity was noted in the in vitro survival and expression of costimulatory, adhesion, and antigen-presenting molecules by B-CLL cells. Spontaneous apoptosis of B-CLL cells in vitro was significantly lower in samples with good prognosis cytogenetics when compared to samples with poor prognosis cytogenetics. In contrast, B-CLL cells from samples with good prognosis cytogenetics exhibited higher basal expression of molecules involved in costimulation, cellular adhesion, and antigen presentation, and induced significantly more T-cell proliferation in mixed lymphocyte cultures. We conclude that chromosomal aberrations of B-CLL cells correlate with the in vitro biological behavior of B-CLL. Our data indicate that good prognosis cytogenetics correlates with less spontaneous apoptosis but greater in vitro immunogenicity. These findings could have significant implications on the design of future therapeutic approaches in patients with CLL, and the likelihood of response based on cytogenetics.
Jahrsdörfer
B
B
Department of Internal Medicine, The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
Wooldridge
J E
JE
Blackwell
S E
SE
Taylor
C M
CM
Link
B K
BK
Weiner
G J
GJ
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002869:Chromosome Aberrations; D003582:Cytogenetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D007770:L-Lactate Dehydrogenase