CD13 expression in B cell malignancies is a hallmark of plasmacytic differentiation
Anna Raimbault
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorSigrid Machherndl-Spandl
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorRaphaël Itzykson
Service d'Hématologie Clinique, Hôpitaux Universitaires Saint Louis, Lariboisière, Fernand Widal, Université Paris Diderot, Paris, France
Search for more papers by this authorSylvain Clauser
Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Boulogne, France
Search for more papers by this authorNicolas Chapuis
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorStéphanie Mathis
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Service d'Hématologie Clinique, Hôpitaux Universitaires Saint Louis, Lariboisière, Fernand Widal, Université Paris Diderot, Paris, France
Search for more papers by this authorJeroen Lauf
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorAnne-Sophie Alary
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorBarbara Burroni
Service d'Anatomopathologie, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorOlivier Kosmider
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorMichaela Fontenay
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorMarie C. Béné
Service d'Hématologie Biologique, CHU et Université de Nantes, Nantes, France
Search for more papers by this authorFrançoise Durrieu
Hématologie Biologique, Institut Bergonié, Bordeaux, France
Search for more papers by this authorPeter Bettelheim
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorCorresponding Author
Valérie Bardet
Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Boulogne, France
Correspondence: Valérie Bardet, Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, 92100 Boulogne, France.
E-mail: [email protected]
Search for more papers by this authorAnna Raimbault
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorSigrid Machherndl-Spandl
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorRaphaël Itzykson
Service d'Hématologie Clinique, Hôpitaux Universitaires Saint Louis, Lariboisière, Fernand Widal, Université Paris Diderot, Paris, France
Search for more papers by this authorSylvain Clauser
Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Boulogne, France
Search for more papers by this authorNicolas Chapuis
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorStéphanie Mathis
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Service d'Hématologie Clinique, Hôpitaux Universitaires Saint Louis, Lariboisière, Fernand Widal, Université Paris Diderot, Paris, France
Search for more papers by this authorJeroen Lauf
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorAnne-Sophie Alary
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorBarbara Burroni
Service d'Anatomopathologie, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorOlivier Kosmider
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorMichaela Fontenay
Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Université Paris Descartes, Paris, France
Search for more papers by this authorMarie C. Béné
Service d'Hématologie Biologique, CHU et Université de Nantes, Nantes, France
Search for more papers by this authorFrançoise Durrieu
Hématologie Biologique, Institut Bergonié, Bordeaux, France
Search for more papers by this authorPeter Bettelheim
Department of Haematology, Internal Oncology and Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen Hospital, Linz, Austria
Search for more papers by this authorCorresponding Author
Valérie Bardet
Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Boulogne, France
Correspondence: Valérie Bardet, Service d'Hématologie-Immunologie-Transfusion, Hôpitaux Universitaires Paris Ile De France Ouest, Université Versailles Saint Quentin, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, 92100 Boulogne, France.
E-mail: [email protected]
Search for more papers by this authorSummary
The diagnosis of Waldenström Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria, including MYD88 L265P mutation. It has been suggested that expression of the myeloid marker CD13 (also termed ANPEP) is more frequent in LPL than in other B-LPD and has also been described on normal and malignant plasma cells. Here, CD13 expression was tested in a cohort of 1037 B-LPD patients from 3 centres by flow cytometry. The percentage of CD13-expressing cells was found to be variable among B-LPD but significantly higher in WM/LPL (median 31% vs. 0% in non-WM/LPL, P < 0·001). In multivariate linear regression, CD13 expression remained significantly associated with a diagnosis of WM/LPL (P < 0·001). A cut-off value of 2% of CD19+ cells co-expressing CD13 yielded the best diagnostic performance for WM/LPL assertion. This was further improved by association with the presence or absence of IgM paraprotein. Finally, given that previously published transcriptomic data revealed no difference in CD13 (also termed ANPEP) mRNA between normal and pathological B-cells, the hypothesis of some post-transcriptional regulation must be favoured. These results suggest that testing for CD13 expression in routine flow cytometry panels could help to discriminate WM/LPL from other B-LPD.
Conflict of interest
The authors declare no conflict of interest.
References
- Agarwal, A. & Ghobrial, I.M. (2013) The bone marrow microenvironment in Waldenstrom macroglobulinemia. Clinical Lymphoma, Myeloma & Leukemia, 13, 218–221.
- Bovio, I.M. & Allan, R.W. (2008) The expression of myeloid antigens CD13 and/or CD33 is a marker of ALK+ anaplastic large cell lymphomas. American Journal of Clinical Pathology, 130, 628–634.
- Cook, J.R., Aguilera, N.I., Reshmi, S., Huang, X., Yu, Z., Gollin, S.M., Abbondanzo, S.L. & Swerdlow, S.H. (2005) Deletion 6q is not a characteristic marker of nodal lymphoplasmacytic lymphoma. Cancer Genetics and Cytogenetics, 162, 85–88.
- Craig, F.E. & Foon, K.A. (2008) Flow cytometric immunophenotyping for hematologic neoplasms. Blood, 111, 3941–3967.
- Gregg, S.L., Gajl-Peczalska, K.J., LeBien, T.W., Bloomfield, C.D., Brunning, R. & Sagawa, K. (1984) Monoclonal antibody MCS-2 as the marker of phorbol diester-induced myeloid differentiation in acute undifferentiated leukemia. Cancer Research, 44, 2724–2730.
- Gutierrez, N.C., Ocio, E.M., de Las Rivas, J., Maiso, P., Delgado, M., Ferminan, E., Arcos, M.J., Sanchez, M.L., Hernandez, J.M. & San Miguel, J.F. (2007) Gene expression profiling of B lymphocytes and plasma cells from Waldenstrom's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals. Leukemia, 21, 541–549.
- Hosmer, D.W., Lemeshow, S. & Sturdivant, R.X. (2013) In: Applied Logistic Regression. Wiley, New York.
- Hunter, Z.R., Branagan, A.R., Manning, R., Patterson, C.J., Santos, D.D., Tournilhac, O., Dorfman, D.M. & Treon, S.P. (2005) CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clinical Lymphoma, 5, 246–249.
- Hunter, Z.R., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., Manning, R.J., Tripsas, C., Patterson, C.J., Sheehy, P. & Treon, S.P. (2014) The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood, 123, 1637–1646.
- Insuasti-Beltran, G., Gale, J.M., Wilson, C.S., Foucar, K. & Czuchlewski, D.R. (2015) Significance of MYD88 L265P mutation status in the subclassification of low-grade B-cell lymphoma/leukemia. Archives of Pathology and Laboratory Medicine, 139, 1035–1041.
- Konoplev, S., Medeiros, L.J., Bueso-Ramos, C.E., Jorgensen, J.L. & Lin, P. (2005) Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. American Journal of Clinical Pathology, 124, 414–420.
- Lauria, F., Raspadori, D., Martinelli, G., Rondelli, D., Ventura, M.A., Farabegoli, P., Tosi, P., Testoni, N., Visani, G., Zaccaria, A., Gamberi, B., Cenacchi, A. & Tura, S. (1994) Increased expression of myeloid antigen markers in adult acute lymphoblastic leukaemia patients: diagnostic and prognostic implications. British Journal of Haematology, 87, 286–292.
- Lin, P., Molina, T.J., Cook, J.R. & Swerdlow, S.H. (2011) Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation. American Journal of Clinical Pathology, 136, 195–210.
- Mina-Osorio, P. (2008) The moonlighting enzyme CD13: old and new functions to target. Trends in Molecular Medicine, 14, 361–371.
- Morice, W.G., Chen, D., Kurtin, P.J., Hanson, C.A. & McPhail, E.D. (2009) Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenstrom's macroglobulinemia. Modern Pathology, 22, 807–816.
- Nakase, K., Kita, K., Shiku, H., Tanaka, I., Nasu, K., Dohy, H., Kyo, T., Tsutani, H. & Kamada, N. (1996) Myeloid antigen, CD13, CD14, and/or CD33 expression is restricted to certain lymphoid neoplasms. American Journal of Clinical Pathology, 105, 761–768.
- O'Brien, R.M. (2007) A caution regarding rules of thumb for variance inflation factors. Quality & Quantity, 41, 673–690.
- Paiva, B., Corchete, L.A., Vidriales, M.B., Garcia-Sanz, R., Perez, J.J., Aires-Mejia, I., Sanchez, M.L., Barcena, P., Alignani, D., Jimenez, C., Sarasquete, M.E., Mateos, M.V., Ocio, E.M., Puig, N., Escalante, F., Hernandez, J., Cuello, R., Garcia de Coca, A., Sierra, M., Montes, M.C., Gonzalez-Lopez, T.J., Galende, J., Barez, A., Alonso, J., Pardal, E., Orfao, A., Gutierrez, N.C. & San Miguel, J.F. (2015) The cellular origin and malignant transformation of Waldenstrom macroglobulinemia. Blood, 125, 2370–2380.
- Pinto, A., Del Vecchio, L., Carbone, A., Roncadin, M., Volpe, R., Serraino, D., Monfardini, S., Colombatti, A. & Zagonel, V. (1991) Expression of myelomonocytic antigens is associated with unfavourable clinicoprognostic factors in B-cell chronic lymphocytic leukaemia. Annals of Oncology, 2 (Suppl 2), 107–113.
- Riemann, D., Kehlen, A., Thiele, K., Lohn, M. & Langner, J. (1997) Induction of aminopeptidase N/CD13 on human lymphocytes after adhesion to fibroblast-like synoviocytes, endothelial cells, epithelial cells, and monocytes/macrophages. Journal of Immunology, 158, 3425–3432.
- Ruiz-Arguelles, G.J. & San Miguel, J.F. (1994) Cell surface markers in multiple myeloma. Mayo Clinic Proceedings, 69, 684–690.
- San Miguel, J.F., Gonzalez, M., Gascon, A., Moro, M.J., Hernandez, J.M., Ortega, F., Jimenez, R., Guerras, L., Romero, M., Casanova, F., Sanz, M.A., Sáanchez, J., Portero, J.A. & Orfao, A. (1991) Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. British Journal of Haematology, 77, 185–190.
- Sobol, R.E., Mick, R., Royston, I., Davey, F.R., Ellison, R.R., Newman, R., Cuttner, J., Griffin, J.D., Collins, H., Nelson, D.A. & Bloomfield, C.D. (1987) Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia. New England Journal of Medicine, 316, 1111–1117.
- Spits, H., Lanier, L.L. & Phillips, J.H. (1995) Development of human T and natural killer cells. Blood, 85, 2654–2670.
- Sun, D. & Ding, A. (2006) MyD88-mediated stabilization of interferon-gamma-induced cytokine and chemokine mRNA. Nature Immunology, 7, 375–381.
- Swerdlow, S.H., Cook, J.R., Sohani, A.R., Pileri, S.A., Harris, N.L., Jaffe, E.S. & Stein, H. (2017) Lymphoplasmacytic lymphoma. In: WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue (ed. by S. Swerdlow, E. Campo, N.L. Harris, E.S. Jaffe, S.A. Pileri, H. Stein, J. Thiele, D. Arber, R. Hasserjian & M. Le Beau), pp. 232. International Agency for Research on Cancer Press, Lyon, France.
- Syrjala, M., Ruutu, T. & Jansson, S.E. (1994) A flow cytometric assay of CD34-positive cell populations in the bone marrow. British Journal of Haematology, 88, 679–684.
- Terre, C., Nguyen-Khac, F., Barin, C., Mozziconacci, M.J., Eclache, V., Leonard, C., Chapiro, E., Farhat, H., Bouyon, A., Rousselot, P., Choquet, S., Spentchian, M., Dubreuil, P., Leblond, V. & Castaigne, S. (2006) Trisomy 4, a new chromosomal abnormality in Waldenstrom's macroglobulinemia: a study of 39 cases. Leukemia, 20, 1634–1636.
- Terstappen, L.W., Johnsen, S., Segers-Nolten, I.M. & Loken, M.R. (1990) Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood, 76, 1739–1747.
- Treon, S.P., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., Sheehy, P., Manning, R.J., Patterson, C.J., Tripsas, C., Arcaini, L., Pinkus, G.S., Rodig, S.J., Sohani, A.R., Harris, N.L., Laramie, J.M., Skifter, D.A., Lincoln, S.E. & Hunter, Z.R. (2012) MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia. New England Journal of Medicine, 367, 826–833.
- Wickstrom, M., Larsson, R., Nygren, P. & Gullbo, J. (2011) Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer Science, 102, 501–508.
- Xu, L., Hunter, Z.R., Yang, G., Zhou, Y., Cao, Y., Liu, X., Morra, E., Trojani, A., Greco, A., Arcaini, L., Varettoni, M., Brown, J.R., Tai, Y.T., Anderson, K.C., Munshi, N.C., Patterson, C.J., Manning, R.J., Tripsas, C.K., Lindeman, N.I. & Treon, S.P. (2013) MYD88 L265P in Waldenstrom macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood, 121, 2051–2058.