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Prognostic factors in CLL

Leukemia Supplements volume 1, pages S29–S30 (2012)Cite this article

Abstract

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, as some patients progress rapidly toward the more advanced studies, whereas others survive for a long period without the need for treatment. This heterogeneity of clinical course was somehow unexplained until studies on the CLL cell features disclosed that the CLL clones were heterogeneous and were characterized by different phenotypic and genotypic features in the different patients. On the basis of these observations, it was determined in retrospective studies that clones characterized by unmutated IGHV genes, and/or CD38 and/or ZAP-70 expression conferred a more severe prognosis to the CLL patients. Here, we present data on prospective studies carried out on Binet A-stage patients, in whom the markers were determined at diagnosis and their predictive value was assessed in comparison with chromosomal abnormalities and gene expression or micro RNA profiles. In addition, hypothesis on the potential pathogenetic role of these markers will be presented.

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References

  1. Chiorazzi N, Rai KR, Ferrarini M . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–815.

    Article  CAS  Google Scholar 

  2. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–5456.

    Article  CAS  Google Scholar 

  3. Cramer P, Hallek M . Prognostic factors in chronic lymphocytic leukemia—what do we need to know? Nat Rev Clin Oncol 2011; 8: 38–47.

    Article  CAS  Google Scholar 

  4. Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840–1847.

    Article  CAS  Google Scholar 

  5. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK . Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 1848–1854.

    Article  CAS  Google Scholar 

  6. Wiestner A, Rosenwald A, Barry TS, Wright G, Davis RE, Henrickson SE et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood 2003; 101: 4944–4951.

    Article  CAS  Google Scholar 

  7. Schroers R, Griesinger F, Trumper L, Haase D, Kulle B, Klein-Hitpass L et al. Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia. Leukemia 2005; 19: 750–758.

    Article  CAS  Google Scholar 

  8. Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004; 363: 105–111.

    Article  CAS  Google Scholar 

  9. Del Giudice I, Morilla A, Osuji N, Matutes E, Morilla R, Burford A et al. Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia. Cancer 2005; 104: 2124–2132.

    Article  CAS  Google Scholar 

  10. Malavasi F, Deaglio S, Damle R, Cutrona G, Ferrarini M, Chiorazzi N . CD38 and chronic lymphocytic leukemia: a decade later. Blood 2011; 118: 3470–3478.

    Article  CAS  Google Scholar 

  11. Hamblin TJ, Orchard JA, Ibbotson RE, Davis Z, Thomas PW, Stevenson FK et al. CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood 2002; 99: 1023–1029.

    Article  CAS  Google Scholar 

  12. Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002; 100: 1410–1416.

    Article  CAS  Google Scholar 

  13. Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348: 1764–1775.

    Article  CAS  Google Scholar 

  14. Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–1916.

    Article  CAS  Google Scholar 

  15. Stilgenbauer S, Sander S, Bullinger L, Benner A, Leupolt E, Winkler D et al. Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica 2007; 92: 1242–1245.

    Article  Google Scholar 

  16. Morabito F, Cutrona G, Gentile M, Matis S, Todoerti K, Colombo M et al. Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia. Br J Haematol 2009; 146: 44–53.

    Article  CAS  Google Scholar 

  17. de Totero D, Meazza R, Zupo S, Cutrona G, Matis S, Colombo M et al. Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells. Blood 2006; 107: 3708–3715.

    Article  CAS  Google Scholar 

  18. Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z et al. The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood 2002; 100: 1215–1219.

    Article  CAS  Google Scholar 

  19. Woyach JA, Lin TS, Lucas MS, Heerema N, Moran ME, Cheney C et al. A phase I/II study of rituximab and etanercept in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. Leukemia 2009; 23: 912–918.

    Article  CAS  Google Scholar 

  20. Bojarska-Junak A, Hus I, Szczepanek EW, Dmoszynska A, Rolinski J . Peripheral blood and bone marrow TNF and TNF receptors in early and advanced stages of B-CLL in correlation with ZAP-70 protein and CD38 antigen. Leuk Res 2008; 32: 225–233.

    Article  CAS  Google Scholar 

  21. Calin GA, Croce CM . Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes. Blood 2009; 114: 4761–4770.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. IRCCS Azienda Ospedaliera Universitaria San Martino IST, Genova, Italy

    M Ferrarini & G Cutrona

  2. Dipartimento di Scienze Mediche, Centro di Ricerca per lo Studio delle Leucemie, Università di Milano, U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milano, Italy

    A Neri

  3. Unità Operativa Complessa di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy

    F Morabito

Authors
  1. M Ferrarini
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  2. G Cutrona
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  3. A Neri
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  4. F Morabito
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Correspondence to M Ferrarini.

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The authors declare no conflict of interest.

Additional information

This article was published as part of a supplement that was supported by Novartis, MSD Italia, Roche, Celgene, GlaxoSmithKline, Sanofi, Gilead, Adienne, Italfarmaco, Pierre Fabre Pharmaceuticals with an unrestricted educational contribution to AREO—Associazione Ricerche Emato-Oncologiche (Genoa) and AMS—Associazione Malattie del Sangue (Milan) for the purpose of advancing research in acute and chronic leukemia.

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Ferrarini, M., Cutrona, G., Neri, A. et al. Prognostic factors in CLL. Leukemia Suppl 1 (Suppl 2), S29–S30 (2012). https://doi.org/10.1038/leusup.2012.17

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