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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4644-4649.
Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-12-4412.

Submitted December 30, 2003
Accepted February 9, 2004
Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders
Marco Ladetto*, Mara Compagno, Irene Ricca, Marco Pagano, Alberto Rocci, Monica Astolfi, Daniela Drandi, Paola Francia di Celle, Maria Dell Aquila, Barbara Mantoan, Sonia Vallet, Gloria Pagliano, Federica De Marco, Roberto Francese, Loredana Santo, Alessandra Cuttica, Carlo Marinone, Mario Boccadoro, and Corrado Tarella
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Universita di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy
Divisione di Anatomia Patologica, Dipartimento di Scienze Biomediche ed Oncologia Umana, Universita di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy
Divisione di Medicina Generale VII, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy
* Corresponding author; email: marco.ladetto{at}unito.it.
In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B cell lymphoproliferative disorders (MBCLD) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% tumor cells. TRF length was evaluated by Southern blot 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 1896-11200 bp) and did not correlate with patient age and sex. TRF length was greater in diffuse large cell, Burkitt's and follicular lymphoma (median: 7789 bp, 9471 bp, 7383 bp, respectively) than in mantle cell lymphoma and chronic lymphocytic leukemia (median: 3582 bp and 4346 bp, respectively). GC-derived MBCLD have the longest telomeres, while those arising from GC-inexperienced cells have 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; 3) the low TRF length of GC-inexperienced MBCLD indicates that these neoplasms are good candidates for treatment with telomerase inhibitors, a class of molecules currently the subject of extensive pre-clinical evaluation.

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