|
|
Blood, 1 April 2006, Vol. 107, No. 7, pp. 2889-2894.
Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-06-2227.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status
Mia Thorsélius,
Alexander Kröber,
Fiona Murray,
Ulf Thunberg,
Gerard Tobin,
Andreas Bühler,
Dirk Kienle,
Emilia Albesiano,
Rossana Maffei,
Lan-Phuong Dao-Ung,
James Wiley,
Juhani Vilpo,
Anna Laurell,
Mats Merup,
Göran Roos,
Karin Karlsson,
Nicholas Chiorazzi,
Roberto Marasca,
Hartmut Döhner,
Stephan Stilgenbauer, and
Richard Rosenquist
From the Department of Genetics and Pathology and the Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden; the Department of Internal Medicine III, University of Ulm, Ulm, Germany; the Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System and Departments of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, NY; the Department of Oncology and Hematology, University of Modena and Reggio E., Modena, Italy; the Department of Medicine, University of Sydney, Nepean Hospital, Penrith, NSW, Australia; the Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland; the Department of Medicine at Karolinska University Hospital, Huddinge, Sweden; the Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden; and the Department of Hematology, Linköping University Hospital, Linköping, Sweden.
We recently reported that Swedish VH3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite VH mutation status. To investigate this further, we analyzed the VH and VL gene rearrangements in 90 VH3-21+ patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated VH genes and 37% unmutated VH genes. Fifty (56%) patients displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif DANGMDV. Also, a highly biased V 2-14 use was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although VH3-21+ CLLs have a remarkably predominant expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the VH3-21+ cohort (median survival, 88 months), with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21+ cases as well as a slight increase of 11q-aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21+ CLLs independent of geographic origin and mutation status.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Hallek, B. D. Cheson, D. Catovsky, F. Caligaris-Cappio, G. Dighiero, H. Dohner, P. Hillmen, M. J. Keating, E. Montserrat, K. R. Rai, 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,
June 15, 2008;
111(12):
5446 - 5456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Ghia, S. Jain, G. F. Widhopf II, L. Z. Rassenti, M. J. Keating, W. G. Wierda, J. G. Gribben, J. R. Brown, K. R. Rai, J. C. Byrd, et al.
Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection
Blood,
May 15, 2008;
111(10):
5101 - 5108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Murray, N. Darzentas, A. Hadzidimitriou, G. Tobin, M. Boudjogra, C. Scielzo, N. Laoutaris, K. Karlsson, F. Baran-Marzsak, A. Tsaftaris, et al.
Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis
Blood,
February 1, 2008;
111(3):
1524 - 1533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Hauswirth and U. Jager
Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia
Haematologica,
January 1, 2008;
93(1):
14 - 19.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bomben, M. Dal Bo, D. Capello, D. Benedetti, D. Marconi, A. Zucchetto, F. Forconi, R. Maffei, E. M. Ghia, L. Laurenti, et al.
Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study
Blood,
April 1, 2007;
109(7):
2989 - 2998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Landgren, J. S. Rapkin, N. E. Caporaso, L. Mellemkjaer, G. Gridley, L. R. Goldin, and E. A. Engels
Respiratory tract infections and subsequent risk of chronic lymphocytic leukemia
Blood,
March 1, 2007;
109(5):
2198 - 2201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Stamatopoulos, C. Belessi, C. Moreno, M. Boudjograh, G. Guida, T. Smilevska, L. Belhoul, S. Stella, N. Stavroyianni, M. Crespo, et al.
Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations
Blood,
January 1, 2007;
109(1):
259 - 270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Krober, H. Dohner, and S. Stilgenbauer
In Reply
J. Clin. Oncol.,
July 1, 2006;
24(19):
3219 - 3220.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Landgren, E. A. Engels, N. E. Caporaso, G. Gridley, L. Mellemkjaer, K. Hemminki, M. S. Linet, and L. R. Goldin
Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries
Blood,
July 1, 2006;
108(1):
292 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
