|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 November 2000, Vol. 96, No. 10, pp. 3569-3577
NEOPLASIA
Extensive genetic alterations of the HLA region,
including homozygous deletions of HLA class
II genes in B-cell lymphomas arising in
immune-privileged sites
Sietske A. Riemersma,
Ekaterina S. Jordanova,
Roelandt F. J. Schop,
Katja Philippo,
Leendert H. J. Looijenga,
Ed Schuuring, and
Philip M. Kluin
From the Department of Pathology, Leiden University
Medical Center, Leiden, The Netherlands; Department of
Pathology, Laboratory for Experimental Patho-Oncology, Josephine
Nefkens Institute, University Hospital Rotterdam, The
Netherlands.
In B-cell lymphomas, loss of human leukocyte antigen (HLA)
class I and II molecules might contribute to immune escape from CD8+ and CD4+ cytotoxic T cells, especially
because B cells can present their own idiotype. Loss of HLA expression
and the possible underlying genomic alterations were studied in 28 testicular, 11 central nervous system, and 21 nodal diffuse large
B-cell lymphomas (DLCLs), the first two sites are considered as
immune-privileged sites. The analysis included immunohistochemistry,
loss of heterozygosity analysis, and fluorescent in situ hybridization
(FISH) on interphase cells and isolated DNA fibers. Total loss of HLA-A
expression was found in 60% of the extranodal cases and in 10% of the
nodal cases (P < .01), whereas loss of HLA-DR expression
was found in 56% and 5%, respectively (P < .01). This
was accompanied by extensive loss of heterozygosity within the HLA
region in the extranodal DLCLs. In 3 cases, retention of heterozygosity
for D6S1666 in the class II region suggested a homozygous deletion.
This finding was confirmed by interphase FISH that showed homozygous
deletions in the class II genes in 11 of the 18 extranodal lymphomas
but in none of the 7 nodal DLCLs (P < .001). Mapping by
fiber FISH showed variable deletions that always included HLA-DQ and
HLA-DR genes. Hemizygous deletions and mitotic recombinations often
involving all HLA genes were found in 13 of 18 extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA class I and II
expression might help the B-cell lymphoma cells to escape from immune attack.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H.-W. Bernd, M. Ziepert, C. Thorns, W. Klapper, H.-H. Wacker, M. Hummel, H. Stein, M.-L. Hansmann, G. Ott, A. Rosenwald, et al.
Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials
Haematologica,
November 1, 2009;
94(11):
1569 - 1580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Montesinos-Rongen, R. Siebert, and M. Deckert
Primary lymphoma of the central nervous system: just DLBCL or not?
Blood,
January 1, 2009;
113(1):
7 - 10.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-C. Chang, G.-C. Huang, D. Jones, and Y.-H. Lin
Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses
Clin. Cancer Res.,
November 15, 2007;
13(22):
6666 - 6672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Booman, J. Douwes, M.-C. Legdeur, J. van Baarlen, E. Schuuring, and P. Kluin
From brain to testis: immune escape and clonal selection in a B cell lymphoma with selective out-growth in two immune sanctuariesy
Haematologica,
June 1, 2007;
92(6):
e69 - e71.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H Veelken, S Vik Dannheim, J Schulte Moenting, U. Martens, J Finke, and A Schmitt-Graeff
Immunophenotype as prognostic factor for diffuse large B-cell lymphoma in patients undergoing clinical risk-adapted therapy
Ann. Onc.,
May 1, 2007;
18(5):
931 - 939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Roberts, G. Wright, A. R. Rosenwald, M. A. Jaramillo, T. M. Grogan, T. P. Miller, Y. Frutiger, W. C. Chan, R. D. Gascoyne, G. Ott, et al.
Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival
Blood,
July 1, 2006;
108(1):
311 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Booman, J. Douwes, A. M. Glas, S. A. Riemersma, E. S. Jordanova, K. Kok, A. Rosenwald, D. de Jong, E. Schuuring, and P. M. Kluin
Mechanisms and Effects of Loss of Human Leukocyte Antigen Class II Expression in Immune-Privileged Site-Associated B-Cell Lymphoma.
Clin. Cancer Res.,
May 1, 2006;
12(9):
2698 - 2705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Rimsza, R. A. Roberts, E. Campo, T. M. Grogan, S. Bea, I. Salaverria, A. Zettl, A. Rosenwald, G. Ott, H. K. Muller-Hermelink, et al.
Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions
Blood,
February 1, 2006;
107(3):
1101 - 1107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Rimsza, R. A. Roberts, T. P. Miller, J. M. Unger, M. LeBlanc, R. M. Braziel, D. D. Weisenberger, W. C. Chan, H. K. Muller-Hermelink, E. S. Jaffe, et al.
Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project
Blood,
June 1, 2004;
103(11):
4251 - 4258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Demanet, A. Mulder, V. Deneys, M. J. Worsham, P. Maes, F. H. Claas, and S. Ferrone
Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack?
Blood,
April 15, 2004;
103(8):
3122 - 3130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Zucca, A. Conconi, T.I. Mughal, A.H. Sarris, J.F. Seymour, U. Vitolo, R. Klasa, M. Ozsahin, G.M. Mead, M.A. Gianni, et al.
Patterns of Outcome and Prognostic Factors in Primary Large-Cell Lymphoma of the Testis in a Survey by the International Extranodal Lymphoma Study Group
J. Clin. Oncol.,
January 1, 2003;
21(1):
20 - 27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Robetorye, S. D. Bohling, J. W. Morgan, G. C. Fillmore, M. S. Lim, and K. S. J. Elenitoba-Johnson
Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)
J. Mol. Diagn.,
August 1, 2002;
4(3):
123 - 136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
