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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
We are sorry, but there is no personal subscription option available for your country.
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Chiorazzi N, Rai KR, Ferrarini M . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–815.
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.
Cramer P, Hallek M . Prognostic factors in chronic lymphocytic leukemia—what do we need to know? Nat Rev Clin Oncol 2011; 8: 38–47.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Calin GA, Croce CM . Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes. Blood 2009; 114: 4761–4770.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
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.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/leusup.2012.17