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.
Ladetto
Marco
M
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
Compagno
Mara
M
Ricca
Irene
I
Pagano
Marco
M
Rocci
Alberto
A
Astolfi
Monica
M
Drandi
Daniela
D
di Celle
Paola Francia
PF
Dell'Aquila
Maria
M
Mantoan
Barbara
B
Vallet
Sonia
S
Pagliano
Gloria
G
De Marco
Federica
F
Francese
Roberto
R
Santo
Loredana
L
Cuttica
Alessandra
A
Marinone
Carlo
C
Boccadoro
Mario
M
Tarella
Corrado
C
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*