Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray

An imbalance between cellular apoptosis and survival may be critical for th e pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node preparations from patients with mantle cell lymphoma (MCL) was compar ed to the pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucl eotide microarray analysis was performed comparing 5 MCLs to 4 HLs using hi gh-density microarrays. The expression data were analyzed using Genespring software. For confirmation, the expression of selected genes was analyzed b y real-time polymerase chain reaction using the RNA extracted from 16 MCL a nd 12 HL samples. The focus was on 42 genes that were at least 3-fold down- regulated in MCL; in addition to the B-cell leukemia 2 (BCL2) system other apoptotic pathways were altered in MCL. The FAS-assoclated via death domain (FADD) gene that acts downstream of the FAS cascade as a key gene to induc e apoptosis was more than 10-fold down-regulated in MCL. Furthermore, the d eath-associated protein 6 (DAXX) gene, the caspase 2 (CASP2) gene, and the RIPK1 domain containing adapter with death domain (RAIDD) gene, which are k ey genes in other proapoptotic pathways, were also decreased in the MCL sam ples. The suggestion is made that in addition to the known overexpression o f cyclin D1, which drives entry into the cell cycle, disturbances of pathwa ys associated with apoptosis contribute to the development of MCL. (C) 2001 by The American Society of Hematology.