Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease

被引:49
作者
Marafioti, T [1 ]
Pozzobon, M
Hansmann, ML
Delsol, G
Pileri, SA
Mason, DY
机构
[1] John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England
[2] John Radcliffe Hosp, Leukaemia Res Fund, Immunodiagnost Unit, Oxford OX3 9DU, England
[3] Univ Frankfurt Klinikum, Senckenberg Inst Pathol, D-6000 Frankfurt, Germany
[4] Ctr Physiopathol Toulouse, INSERM, U563, Toulouse, France
[5] Policlin S Orsola, Ist Ematol & Oncol Med L&A Seragnoli, Serv Ematopatol, Cattedra Anat Patol, Bologna, Italy
关键词
D O I
10.1182/blood-2003-05-1487
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The neoplastic cells in classical Hodgkin disease (Reed-Sternberg cells) are of B-lymphoid origin, but they lack many markers of this cell lineage, for example, immunoglobulin, CD20, and B-cell-associated transcription factors. In contrast, the neoplastic cells ("L&H" cells) in lymphocyte predominance Hodgkin disease retain the molecular profile of germinal center B cells. In this paper, we investigated the expression in Hodgkin disease (45 cases and 3 cell lines) of 5 intracellular signaling molecules found in B. cells. The Src family kinase Syk, the B-cell adaptor protein BLNK, and phospholipase C (PLC)-gamma2 were consistently absent from Reed-Sternberg cells, whereas 2 other Src kinases (Lyn and Fyn) were heterogeneously expressed in a proportion of cases (12% and 42%, respectively). In contrast, the tumor cells in all cases of lymphocyte predominance Hodgkin disease were positive for Fyn, Syk, BLNK, and PLC-gamma2, and Lyn immunostaining was seen in a minority of biopsies. These results indicate that in Reed-Sternberg cells, the defect in B-cell lineage marker expression includes a spectrum of molecules involved in intracellular signaling, a finding in keeping with recent gene expression profiling studies. Furthermore, the clear difference in expression of signaling proteins between the 2 major subtypes of Hodgkin disease may be of diagnostic value.
引用
收藏
页码:188 / 193
页数:6
相关论文
共 46 条
[1]  
[Anonymous], PRACT APPROACH SER
[2]   Constitutive nuclear factor-κB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells [J].
Bargou, RC ;
Emmerich, F ;
Krappmann, D ;
Bommert, K ;
Mapara, MY ;
Arnold, W ;
Royer, HD ;
Grinstein, E ;
Greiner, A ;
Scheidereit, C ;
Dörken, B .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (12) :2961-2969
[3]   Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease, represent clonal populations of germinal center-derived tumor B cells [J].
Braeuninger, A ;
Kuppers, R ;
Strickler, JG ;
Wacker, HH ;
Rajewsky, K ;
Hansmann, ML .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (17) :9337-9342
[4]  
Bräuninger A, 2003, CANCER RES, V63, P1644
[5]   NEW NOMENCLATURE FOR THE RETH MOTIF (OR ARH1/TAM/ARAM/YXXL) [J].
CAMBIER, JC ;
DAERON, M ;
FRIDMAN, W ;
GERGELY, J ;
KINET, JP ;
KLAUSNER, R ;
LYNCH, R ;
MALISSEN, B ;
PECHT, I ;
REINHERZ, E ;
RAVETCH, J ;
RETH, M ;
SAMELSON, L ;
SANDOR, M ;
SCHREIBER, A ;
SEED, B ;
TERHORST, C ;
VANDEWINKEL, J ;
WEISS, A .
IMMUNOLOGY TODAY, 1995, 16 (02) :110-110
[6]  
Carbone A, 1998, BLOOD, V92, P2220
[7]   Reed-Sternberg cells of classical Hodgkin's disease react with the plasma cell-specific monoclonal antibody B-B4 and express human syndecan-1 [J].
Carbone, A ;
Gloghini, A ;
Gattei, V ;
Degan, M ;
Improta, S ;
Aldinucci, D ;
Canzonieri, V ;
Perin, T ;
Volpe, R ;
Gaidano, G ;
Zagonel, V ;
Pinto, A .
BLOOD, 1997, 89 (10) :3787-3794
[8]   Expression of BCL-6 protein and CD138/syndecan-1 as B-cell markers in Hodgkin's disease [J].
Carbone, A ;
Gloghini, A ;
Gaidano, G .
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, 1999, 14 (03) :144-148
[9]   Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes [J].
Chan, VWF ;
Lowell, CA ;
DeFranco, AL .
CURRENT BIOLOGY, 1998, 8 (10) :545-553
[10]   Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation [J].
Chan, VWF ;
Meng, FY ;
Soriano, P ;
DeFranco, AL ;
Lowell, CA .
IMMUNITY, 1997, 7 (01) :69-81