Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients.
Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465-16 762); (2) TRF-L correlates to VH-MS (r(2)=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as 'discordant'; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.
Ricca
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I
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale--Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy. irene.ricca@libero.it
Rocci
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A
Drandi
D
D
Francese
R
R
Compagno
M
M
Lobetti Bodoni
C
C
De Marco
F
F
Astolfi
M
M
Monitillo
L
L
Vallet
S
S
Calvi
R
R
Ficara
F
F
Omedè
P
P
Rosato
R
R
Gallamini
A
A
Marinone
C
C
Bergui
L
L
Boccadoro
M
M
Tarella
C
C
Ladetto
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M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D018572:Disease-Free Survival; D006801:Humans; D007135:Immunoglobulin Variable Region; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016615:Telomere / Q000648:ultrastructure*
D007135:Immunoglobulin Variable Region