Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms

被引:16
作者
Natkunam, Yasodha [1 ]
Vainer, Gilad [2 ]
Chen, Jun [3 ]
Zhao, Shuchun [1 ]
Marinelli, Robert J. [4 ]
Hammer, Anne S. [5 ]
Hamilton-Dutoit, Stephen [5 ]
Pikarsky, Eli [6 ]
Amir, Gail [6 ]
Levy, Ronald [7 ]
Yisraeli, Joel K. [2 ]
Lossos, Izidore S. [3 ]
机构
[1] Stanford Univ, Sch Med, Pathol, Stanford, CA 94305 USA
[2] Hebrew Univ Hadassah Med Sch, Anat & Cell Biol, Jerusalem, Israel
[3] Univ Miami, Sylvester Comprehens Canc Ctr, Div Hematol Oncol & Mol & Cellular Pharmacol, Med, Miami, FL 33136 USA
[4] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA USA
[5] Aarhus Univ Hosp, Pathol, Aarhus, Denmark
[6] Hadassah Med Ctr, Pathol, Jerusalem, Israel
[7] Stanford Univ, Sch Med, Div Oncol, Med, Stanford, CA 94305 USA
基金
以色列科学基金会;
关键词
IMP; germinal center; diffuse large B-cell lymphoma; tissue microarray; immunohistochemistry;
D O I
10.3324/haematol.10724
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and Objectives VICKZ family members are RNA-binding regulatory proteins expressed during embryogenesis but not usually found in normal adult tissue. The presence of VICKZ in normal germinal centers (GC) prompted us to characterize the expression pattern of this protein in lymphoid and hematopoietic tissues. Design and Methods We generated a pan-VICKZ antibody that recognized all three isoforms of VICKZ protein and screened 889 patients' samples by immunohistologic methods. We also analyzed the expression of VICKZ in normal hematopoiesis tissue by staining samples of tonsils, lymph nodes Results VICKZ protein expression was documented for the first time in normal human GC and in follicular (126/165), mediastinal large B-cell (9/10), Burkitt (2/2), diffuse large B-cell (DLBCL, 155/200), lymphocyte-predominant Hodgkin's (12/13), classical Hodgkin's (101/108), and anaplastic large cell (6/8) lymphomas and in lymphoid and myeloid leukemias. Since DLBCL may derive from GC or non-GC B cells we performed hierarchical cluster analysis for VICKZ, HGAL, BCL6, CD10, MUM1/IRF4 and BCL2 which showed that VICKZ is expressed in both subtypes. In addition, VICKZ mRNA isoforms were differentially expressed in lymphoma subtypes and over 40% of DLBCL expressed hVICKZ2, an isoform not usually present in normal GC B cells. Interpretation and Conclusions We show that in normal lymphoid tissues VICKZ is expressed in GC lymphocytes but in lymphoid neoplasms its expression is not limited to GC-derived lymphoma subtypes. However, VICKZ exhibits differential expression in lymphoma subtypes and thus may be a marker of potential value in the diagnosis and study of hematopoietic neoplasia. The aberrant expression of its isoforms in DLBCL raises the possibility that these isoforms may be associated with different functions and suggests that further study of their role in normal and neoplastic lymphoid cells is warranted.
引用
收藏
页码:176 / 183
页数:8
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