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  • Original Article
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Lymphoma

Identification of MNDA as a new marker for nodal marginal zone lymphoma

Abstract

Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL.

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References

  1. Goldberger A, Brewer G, Hnilica LS, Briggs RC . Nonhistone protein antigen profiles of five leukemic cell lines reflect the extent of myeloid differentiation. Blood 1984; 63: 701–710.

    CAS  PubMed  Google Scholar 

  2. Johnstone RW, Trapani JA . Transcription and growth regulatory functions of the HIN-200 family of proteins. Mol Cell Biol 1999; 19: 5833–5838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Goldberger A, Hnilica LS, Casey SB, Briggs RC . Properties of a nuclear protein marker of human myeloid cell differentiation. J Biol Chem 1986; 261: 4726–4731.

    CAS  PubMed  Google Scholar 

  4. Cousar JB, Briggs RC . Expression of human myeloid cell nuclear differentiation antigen (MNDA) in acute leukemias. Leuk Res 1990; 14: 915–920.

    Article  CAS  PubMed  Google Scholar 

  5. Geng Y, Choubey D . Differential induction of the 200-family proteins in Daudi Burkitt's lymphoma cells by interferon-alpha. J Biol Regul Homeost Agents 2000; 14: 263–268.

    CAS  PubMed  Google Scholar 

  6. Miranda RN, Briggs RC, Shults K, Kinney MC, Jensen RA, Cousar JB . Immunocytochemical analysis of MNDA in tissue sections and sorted normal bone marrow cells documents expression only in maturing normal and neoplastic myelomonocytic cells and a subset of normal and neoplastic B lymphocytes. Hum Pathol 1999; 30: 1040–1049.

    Article  CAS  PubMed  Google Scholar 

  7. Joshi AD, Hegde GV, Dickinson JD, Mittal AK, Lynch JC, Eudy JD, Armitage JO, Bierman PJ, Bociek RG, Devetten MP, Vose JM, Joshi SS . ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res 2007; 13: 5295–5304.

    Article  CAS  PubMed  Google Scholar 

  8. Tracey L, Pérez-Rosado A, Artiga MJ, Camacho FI, Rodríguez A, Martínez N, Ruiz-Ballesteros E, Mollejo M, Martinez B, Cuadros M, Garcia JF, Lawler M, Piris MA . Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. J Pathol 2005; 206: 123–134.

    Article  CAS  PubMed  Google Scholar 

  9. Tracey L, Spiteri I, Ortiz P, Lawler M, Piris MA, Villuendas R . Transcriptional response of T cells to IFN-alpha: changes induced in IFN-alpha-sensitive and resistant cutaneous T cell lymphoma. J Interferon Cytokine Res 2004; 24: 185–195.

    Article  CAS  PubMed  Google Scholar 

  10. Tracey L, Villuendas R, Dotor AM, Spiteri I, Ortiz P, Garcia JF, Peralto JL, Lawler M, Piris MA . Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study. Blood 2003; 102: 1042–1050.

    Article  CAS  PubMed  Google Scholar 

  11. Kallioniemi OP, Wagner U, Kononen J, Sauter G . Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet 2001; 10: 657–662.

    Article  CAS  PubMed  Google Scholar 

  12. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, 2008.

    Google Scholar 

  13. Camacho FI, Algara P, Mollejo M, García JF, Montalbán C, Martínez N, Sánchez-Beato M, Piris MA . Nodal marginal zone lymphoma: a heterogeneous tumor: a comprehensive analysis of a series of 27 cases. Am J Surg Pathol 2003; 27: 762–771.

    Article  PubMed  Google Scholar 

  14. Marafioti T, Jones M, Facchetti F, Diss TC, Du MQ, Isaacson PG, Pozzobon M, Pileri SA, Strickson AJ, Tan SY, Watkins F, Mason DY . Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology. Blood 2003; 102: 2868–2876.

    Article  CAS  PubMed  Google Scholar 

  15. Gellrich S, Ventura R, Jones M, Tan SY, Mason DY . Immunofluorescent and FISH analysis of skin biopsies. Am J Dermatopathol 2004; 26: 242–247.

    Article  PubMed  Google Scholar 

  16. Mason DY, Micklem K, Jones M . Double immunofluorescence labelling of routinely processed paraffin sections. J Pathol 2000; 191: 452–461.

    Article  CAS  PubMed  Google Scholar 

  17. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A . Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000; 102: 565–575.

    Article  CAS  PubMed  Google Scholar 

  18. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T . Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000; 102: 553–563.

    Article  CAS  PubMed  Google Scholar 

  19. Willenbrock K, Jungnickel B, Hansmann ML, Kuppers R . Human splenic marginal zone B cells lack expression of activation-induced cytidine deaminase. Eur J Immunol 2005; 35: 3002–3007.

    Article  CAS  PubMed  Google Scholar 

  20. Mollejo M, Rodríguez-Pinilla MS, Montes-Moreno S, Algara P, Dogan A, Cigudosa JC, Juarez R, Flores T, Forteza J, Arribas A, Piris MA . Splenic Follicular Lymphoma: Clinicopathologic Characteristics of a Series of 32 Cases. Am J Surg Pathol 2009; 33: 730–738.

    Article  PubMed  Google Scholar 

  21. Ludlow LE, Johnstone RW, Clarke CJ . The HIN-200 family: more than interferon-inducible genes? Exp Cell Res 2005; 308: 1–17.

    Article  CAS  PubMed  Google Scholar 

  22. Liu T, Rojas A, Ye Y, Godzik A . Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family. Protein Sci 2003; 12: 1872–1881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Reed JC, Doctor K, Rojas A, Zapata JM, Stehlik C, Fiorentino L, Damiano J . Comparative analysis of apoptosis and inflammation genes of mice and humans. Genome Res 2003; 13: 1376–1388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pawlowski K, Pio F, Chu Z, Reed JC, Godzik A . PAAD—a new protein domain associated with apoptosis, cancer and autoimmune diseases. Trends Biochem Sci 2001; 26: 85–87.

    Article  CAS  PubMed  Google Scholar 

  25. Staub E, Dahl E, Rosenthal A . The DAPIN family: a novel domain links apoptotic and interferon response proteins. Trends Biochem Sci 2001; 26: 83–85.

    Article  CAS  PubMed  Google Scholar 

  26. Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, Tchernia G, Steiniger B, Staudt LM, Casanova JL, Reynaud CA, Weill JC . Human blood IgM ‘memory’ B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 2004; 104: 3647–3654.

    Article  CAS  PubMed  Google Scholar 

  27. Pillai S, Cariappa A, Moran ST . Marginal zone B cells. Annu Rev Immunol 2005; 23: 161–196.

    Article  CAS  PubMed  Google Scholar 

  28. Algara P, Mateo MS, Sanchez-Beato M, Mollejo M, Navas IC, Romero L, Solé F, Salido M, Florensa L, Martínez P, Campo E, Piris MA . Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood 2002; 99: 1299–1304.

    Article  CAS  PubMed  Google Scholar 

  29. Chiorazzi N, Rai KR, Ferrarini M . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–815.

    Article  CAS  PubMed  Google Scholar 

  30. Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Takeshita M, Kikuchi M, Nakamura N, Takasu O, Arakawa F, Tagawa H, Seto M, Ohshima K . CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. Blood 2007; 109: 3076–3079.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study is supported by grants from the Ministerio de Sanidad y Consumo (RETICS, FIS PI052742, PI052800, INT07/028), Ministerio de Ciencia e Innovación (SAF2008-03871) and the Servicio de Salud de Castilla la Mancha (SESCAM 06047-00, FISCAM GCS-2006-C/06), Spain. All the antibodies described here, produced at CNIO, are available to others for scientific use in research.

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Correspondence to M A Piris.

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Kanellis, G., Roncador, G., Arribas, A. et al. Identification of MNDA as a new marker for nodal marginal zone lymphoma. Leukemia 23, 1847–1857 (2009). https://doi.org/10.1038/leu.2009.108

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