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


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.


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.
Natkunam
Yasodha
Y
Pathology, Stanford University School of Medicine, Stanford, CA, USA. Ilossos@med.miami.edu
Vainer
Gilad
G
Chen
Jun
J
Zhao
Shuchun
S
Marinelli
Robert J
RJ
Hammer
Anne S
AS
Hamilton-Dutoit
Stephen
S
Pikarsky
Eli
E
Amir
Gail
G
Levy
Ronald
R
Yisraeli
Joel K
JK
Lossos
Izidore S
IS
D016475:3T3 Cells; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006367:HeLa Cells; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology
D016601:RNA-Binding Proteins