Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders.
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.
Cattedra di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Azienda Ospedaliera San Giovanni Battista, Via Genova 3, 10126 Turin, Italy. marco.ladetto@unito.it
Marco
M
Ladetto
Mara
M
Compagno
Irene
I
Ricca
Marco
M
Pagano
Alberto
A
Rocci
Monica
M
Astolfi
Daniela
D
Drandi
Paola Francia
PF
di Celle
Maria
M
Dell'Aquila
Barbara
B
Mantoan
Sonia
S
Vallet
Gloria
G
Pagliano
Federica
F
De Marco
Roberto
R
Francese
Loredana
L
Santo
Alessandra
A
Cuttica
Carlo
C
Marinone
Mario
M
Boccadoro
Corrado
C
Tarella
D001402:B-Lymphocytes / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology*; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D015183:Restriction Mapping; D016615:Telomere / Q000473:pathology / Q000648:ultrastructure*