Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosis-associated genes.
The B-cell lymphoproliferative malignancies B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) share characteristics, including overlapping chromosomal aberrations with deletions on chromosome bands 13q14, 11q23, 17p13, and 6q21 and gains on chromosome bands 3q26, 12q13, and 8q24. To elucidate the biochemical processes involved in the pathogenesis of B-CLL and MCL, we analyzed the expression level of a set of genes that play central roles in apoptotic or cell proliferation pathways and of candidate genes from frequently altered genomic regions, namely ATM, BAX, BCL2, CCND1, CCND3, CDK2, CDK4, CDKN1A, CDKN1B, E2F1, ETV5, MYC, RB1, SELL, TFDP2, TNFSF10, and TP53. Performing real-time quantitative reverse transcription polymerase chain reaction in a panel of patients with MCL and B-CLL and control samples, significant overexpression and underexpression was observed for most of these genes. Statistical analysis of the expression data revealed the combination of CCND1 and CDK4 as the best classifier concerning separation of both lymphoma types. Overexpression in these malignancies suggests ETV5 as a new candidate for a pathogenic factor in B-cell lymphomas. Characteristic deregulation of multiple genes analyzed in this study could be combined in a comprehensive picture of 2 distinctive pathomechanisms in B-CLL and MCL. In B-CLL, the expression parameters are in strong favor of protection of the malignant cells from apoptosis but did not provide evidence for promoting cell cycle. In contrast, in MCL the impairment of apoptosis induction seems to play a minor role, whereas most expression data indicate an enhancement of cell proliferation.
Korz
Christian
C
Abteilung Molekulare Genetik and Zentrale Einheit Biostatistik, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Pscherer
Armin
A
Benner
Axel
A
Mertens
Daniel
D
Schaffner
Claudia
C
Leupolt
Elke
E
Döhner
Hartmut
H
Stilgenbauer
Stephan
S
Lichter
Peter
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D054714:Echinocandins; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D018816:Genes, cdc; D005964:Glucosyltransferases; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000209:etiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D054714:Echinocandins; D005656:Fungal Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005964:Glucosyltransferases; C091618:FKS1 protein, S cerevisiae; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases