Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Ladetto M,Compagno M,Ricca I,Pagano M,Rocci A,Astolfi M,Drandi D,di Celle PF,Dell'Aquila M,Mantoan B,Vallet S,Pagliano G,De Marco F,Francese R,Santo L,Cuttica A,Marinone C,Boccadoro M,Tarella Cdoi
10.1182/blood-2003-12-4412subject
Has Abstractpub_date
2004-06-15 00:00:00pages
4644-9issue
12eissn
0006-4971issn
1528-0020pii
2003-12-4412journal_volume
103pub_type
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