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Chronic Lymphocytic Leukemia

Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients

Leukemia volume 21, pages 697–705 (2007)Cite this article

Abstract

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 (r2=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.

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Acknowledgements

This work was supported in part by Compagnia di San Paolo, Turin, Italy, by Ministero dell’ Università e della Ricerca (MIUR) and by Regione Piemonte. IR was recipient of a fellowship from Fondazione Italiana Ricerca sul Cancro (FIRC), Milan, Italy. AR is recipient of a Research Fellowship from the Fondazione Internazionale di Ricerca in Medicina Sperimentale, Turin, Italy. MC was recipient of a fellowship from Fondazione Angela Bossolasco, Turin, Italy.

Contributions: I Ricca designed and performed the research, analyzed data and wrote the paper. A Rocci and C Lobetti Bodoni performed research and analyzed data. D Drandi, R Francese, M Compagno, M Astolfi, L Monitillo and P Omedè performed research. F De Marco, S Vallet, R Calvi, F Ficara, A Gallamini, C Marinone, L Bergui, M Boccadoro and C Tarella contributed patients. M Ladetto designed the research, contributed vital new reagents, analyzed data and wrote the paper.

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Authors and Affiliations

  1. Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale – Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy

    I Ricca, A Rocci, D Drandi, R Francese, M Compagno, C Lobetti Bodoni, F De Marco, M Astolfi, L Monitillo, S Vallet, P Omedè, L Bergui, M Boccadoro, C Tarella & M Ladetto

  2. Divisione di Ematologia, Ospedale Santa Croce e Carle, Cuneo, Italy

    R Calvi & A Gallamini

  3. Divisione di Medicina Generale VII – Azienda Ospedaliera S. Giovanni Battista, Torino, Italy

    F Ficara & C Marinone

  4. Dipartimento di Science Biomediche Servizio di Epidemiologia dei Tumori e Biostatistica, Centro di Ricerca in Medicina Sperimentale, Università di Torino, Torino, Italy

    R Rosato

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Correspondence to I Ricca.

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Ricca, I., Rocci, A., Drandi, D. et al. Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients. Leukemia 21, 697–705 (2007). https://doi.org/10.1038/sj.leu.2404544

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