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

Yasodha Natkunam, Gilad Vainer, Jun Chen, Shuchun Zhao, Robert J. Marinelli, Anne S. Hammer, Stephen Hamilton-Dutoit, Eli Pikarsky, Gail Amir, Ronald Levy, Joel K. Yisraeli, Izidore Lossos

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 sub-types. 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.

Original languageEnglish
JournalHaematologica
Volume92
Issue number2
StatePublished - Feb 1 2007

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Germinal Center
RNA-Binding Proteins
Hematologic Neoplasms
Lymphoma
Protein Isoforms
B-Lymphocytes
Lymphoid Tissue
Lymphocytes
Hodgkin Disease
RNA Isoforms
Lymphoid Leukemia
Myeloid Leukemia
Palatine Tonsil
Hematopoiesis
Embryonic Development
Cluster Analysis
Neoplasms
Proteins
Lymph Nodes
Staining and Labeling

Keywords

  • Diffuse large B-cell lymphoma
  • Germinal center
  • Immunohistochemistry
  • IMP
  • Tissue microarray

ASJC Scopus subject areas

  • Hematology

Cite this

Natkunam, Y., Vainer, G., Chen, J., Zhao, S., Marinelli, R. J., Hammer, A. S., ... Lossos, I. (2007). Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms. Haematologica, 92(2).

Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms. / Natkunam, Yasodha; Vainer, Gilad; Chen, Jun; Zhao, Shuchun; Marinelli, Robert J.; Hammer, Anne S.; Hamilton-Dutoit, Stephen; Pikarsky, Eli; Amir, Gail; Levy, Ronald; Yisraeli, Joel K.; Lossos, Izidore.

In: Haematologica, Vol. 92, No. 2, 01.02.2007.

Research output: Contribution to journalArticle

Natkunam, Y, Vainer, G, Chen, J, Zhao, S, Marinelli, RJ, Hammer, AS, Hamilton-Dutoit, S, Pikarsky, E, Amir, G, Levy, R, Yisraeli, JK & Lossos, I 2007, 'Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms', Haematologica, vol. 92, no. 2.
Natkunam Y, Vainer G, Chen J, Zhao S, Marinelli RJ, Hammer AS et al. Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms. Haematologica. 2007 Feb 1;92(2).
Natkunam, Yasodha ; Vainer, Gilad ; Chen, Jun ; Zhao, Shuchun ; Marinelli, Robert J. ; Hammer, Anne S. ; Hamilton-Dutoit, Stephen ; Pikarsky, Eli ; Amir, Gail ; Levy, Ronald ; Yisraeli, Joel K. ; Lossos, Izidore. / Expression of the RNA-binding protein VICKZ in normal hematopoietic tissues and neoplasms. In: Haematologica. 2007 ; Vol. 92, No. 2.
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abstract = "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 sub-types. 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.",
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AU - Zhao, Shuchun

AU - Marinelli, Robert J.

AU - Hammer, Anne S.

AU - Hamilton-Dutoit, Stephen

AU - Pikarsky, Eli

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AU - Levy, Ronald

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AU - Lossos, Izidore

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