Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders

• Published in: Blood Vol. 103; no. 12; pp. 4644 - 4649
• Main Authors: Ladetto, Marco, Compagno, Mara, Ricca, Irene, Pagano, Marco, Rocci, Alberto, Astolfi, Monica, Drandi, Daniela, di Celle, Paola Francia, Dell’Aquila, Maria, Mantoan, Barbara, Vallet, Sonia, Pagliano, Gloria, De Marco, Federica, Francese, Roberto, Santo, Loredana, Cuttica, Alessandra, Marinone, Carlo, Boccadoro, Mario, Tarella, Corrado
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.06.2004; The Americain Society of Hematology
• Subjects: B-Lymphocytes - pathology; Biological and medical sciences; Hematologic and hematopoietic diseases; Humans; Leukemia - genetics; Leukemia - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoproliferative Disorders - genetics; Lymphoproliferative Disorders - pathology; Medical sciences; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Restriction Mapping; Telomere - pathology; Telomere - ultrastructure; Human; Immunoglobulins; Restriction fragment length polymorphism; Gene; Germinative center; Pathogenesis; Lymphoproliferative syndrome; Malignant hemopathy; B-Lymphocyte; Mutation; Carcinogenesis; Telomere
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2003-12-4412

In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B-cell lymphoproliferative disorders (MBCLDs) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% or more tumor cells. TRF length was evaluated by Southern blot analysis using a chemiluminescence-based assay. GC status was assessed through screening for stable and ongoing somatic mutations within the immunoglobulin heavy-chain genes. Median TRF length was 6170 bp (range, 1896-11 200 bp) and did not correlate with patient age or sex. TRF length was greater in diffuse large cell lymphoma, Burkitt lymphoma, and follicular lymphoma (medians: 7789 bp, 9471 bp, and 7383 bp, respectively) than in mantle cell lymphoma and chronic lymphocytic leukemia (medians: 3582 bp and 4346 bp, respectively). GC-derived MBCLDs had the longest telomeres, whereas those arising from GC-inexperienced cells had the shortest (P < 10-9). We conclude that (1) TRF length in MBCLD is highly heterogeneous; (2) GC-derived tumors have long telomeres, suggesting that minimal telomere erosion occurs during GC-derived lymphomagenesis; and (3) the short TRF lengths of GC-inexperienced MBCLDs indicates that these neoplasms are good candidates for treatment with telomerase inhibitors, a class of molecules currently the subject of extensive preclinical evaluation. (Blood. 2004;103:4644-4649)