Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders. The percentage of CD2-, CD25+ and/or CD30+ MC was considerably lower in patients with indolent SM compared to patients with advanced SM, including aggressive SM and MC leukemia. Whereas CD25 and CD30 expression in MC could not be associated with prognosis, we found that lack of CD2 expression in MC is associated with a significantly reduced overall survival (OS) in patients with SM (p < 0.0001). Lack of CD2 was also associated with the presence of extramedullary involvement affecting the spleen, liver, and/or lymph nodes (odds ratio 2.63 compared to SM with CD2+ MC). Together, lack of CD2 expression in MC is a prognostic marker and indicator of reduced OS and extramedullary disease expansion in patients with SM.

Allergy Unit Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy

Brno University Hospital Brno Czech Republic

Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf Aachen Germany and Department of Haematology Oncology Haemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen Aachen Germany

Department for Hematology and Oncology Universitätsklinikum Schleswig Holstein and University Cancer Center Schleswig Holstein Lübeck Germany

Department of Allergology Medical University of Gdansk Gdansk Poland

Department of Clinical Chemistry University Hospital Bern Inselspital Bern Switzerland

Department of Hematology and Oncology University Hospital Mannheim Heidelberg University Mannheim Germany

Department of Hematology Bone Marrow Transplant Unit Carol Davila University of Medicine and Pharmacy Emergency University Hospital Bucharest Romania

Department of Hematology Luzerner Kantonsspital University of Luzern Luzern Switzerland

Department of Hematology Semmelweis University Budapest Hungary

Department of Hematology Uppsala University Hospital and Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Internal Medicine 1 Division of Hematology and Hemostaseology Medical University of Vienna Vienna Austria

Department of Internal Medicine Erasmus University Rotterdam Rotterdam The Netherlands

Department of Medicine 1 Medical Center University of Freiburg Faculty of Medicine Freiburg Germany

Department of Respiratory Medicine and Allergy Karolinska University Hospital Huddinge Stockholm; and Department of Medicine Solna Division of Immunology and Allergy Karolinska Institutet Stockholm Sweden

Departments of Hematology and Pharmacology Oslo University Hospital Rikshospitalet Oslo Norway

Division of Allergy and Clinical Immunology University of Salerno Salerno Italy

Division of Hematology Istanbul Medical School University of Istanbul Istanbul Turkey

German Cancer Consortium Heidelberg Germany

Hôpital Necker Imagine Institute INSERM U1163 University of Sorbonne Paris Cité Centre national de référence des mastocytoses Paris France

Kantonsspital Aarau AG Medizinische Universitätsklinik Hämatologie Aarau Switzerland

Klinik für Dermatologie und Venerologie Kepler Universitätsklinikum Linz Austria

Klinik für Innere Medizin 3 Schwerpunkt Hämatologie und Onkologie Kepler Universitätsklinikum Linz Austria

Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein; Technische Universität München München Germany

KU Leuven Department of Microbiology Immunology and Transplantation Allergy and Clinical Immunology Research Group and MASTeL UZ Leuven Leuven Belgium

Ludwig Boltzmann Institute for Hematology and Oncology Medical University of Vienna Vienna Austria

Mastocytosis Center Attikon University Hospital of Athens Athens Greece

Medical Clinic 1 Universitätsklinikum Leipzig AöR Leipzig Germany

Pediatric Dermatology Internal Medicine Azienda Ospedaliera Università di Padova Padova Italy

Policlinico San Matteo Pavia Fondazione IRCCS Pavia Italy

S C Ematologia Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Stanford Cancer Institute Stanford University School of Medicine Stanford CA USA

Universitätsklinik für Dermatologie und Venerologie Medical University of Graz Graz Austria

Universitätsspital Basel Basel Switzerland

Universiteit Antwerpen Campus Drie Eiken Antwerp Belgium

University Medical Center Groningen University of Groningen Groningen The Netherlands

University of California San Francisco CA USA

Zobrazit více v PubMed

Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603–25. PubMed

Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37:435–53. PubMed

Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373:163–72. PubMed

Valent P, Akin C, Hartmann K, Alvarez-Twose I, Brockow K, Hermine O, et al. Updated diagnostic criteria and classification of mast cell disorders: a consensus proposal. HemaSphere. 2021;5:e646. PubMed PMC

Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolympoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36:1703–19. PubMed PMC

Valent P, Sotlar K, Horny HP, Arock M, Akin C. World Health Organization Classification and Diagnosis of Mastocytosis: Update 2023 and Future Perspectives. Immunol Allergy Clin North Am. 2023;432:627–49. PubMed

Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka H-M, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200–28. PubMed PMC

Tsai M, Valent P, Galli SJ. KIT as a master regulator of the mast cell lineage. J Allergy Clin Immunol. 2022;149:1845–54. PubMed PMC

Chantran Y, Valent P, Arock M. KIT mutations and other genetic defects in mastocytosis: implications for disease pathology and targeted therapies. Immunol Allergy Clin North Am. 2023;43:651–64. PubMed

Valent P, Hoermann G, Bonadonna P, Hartmann K, Sperr WR, Broesby-Olsen S, et al. The normal range of baseline tryptase should be 1 to 15 ng/ml and covers healthy individuals with HαT. J Allergy Clin Immunol Pr. 2023;11:3010–20. PubMed PMC

Hauswirth AW, Florian S, Schernthaner GH, Krauth MT, Sonneck K, Sperr WR, et al. Expression of cell surface antigens on mast cells: mast cell phenotyping. Methods Mol Biol. 2006;315:77–90. PubMed

Sánchez-Muñoz L, Teodósio C, Morgado JM, Escribano L. Immunophenotypic characterization of bone marrow mast cells in mastocytosis and other mast cell disorders. Cell Biol. 2011;103:333–59. PubMed

Sánchez-Muñoz L, Teodosio C, Morgado JM, Perbellini O, Mayado A, Alvarez-Twose I, et al. Flow cytometry in mastocytosis: utility as a diagnostic and prognostic tool. Immunol Allergy Clin North Am. 2014;34:297–313. PubMed

Escribano L, Orfao A, Díaz-Agustin B, Villarrubia J, Cerveró C, López A, et al. Indolent systemic mast cell disease in adults: immunophenotypic characterization of bone marrow mast cells and its diagnostic implications. Blood. 1998;91:2731–6. PubMed

Escribano L, Díaz-Agustín B, Bellas C, Navalón R, Nuñez R, Sperr WR, et al. Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis. Leuk Res. 2001;25:563–70. PubMed

Valent P, Schernthaner GH, Sperr WR, Fritsch G, Agis H, Willheim M, et al. Variable expression of activation-linked surface antigens on human mast cells in health and disease. Immunol Rev. 2001;179:74–81. PubMed

Schernthaner GH, Jordan JH, Ghannadan M, Agis H, Bevec D, Nuñez R, et al. Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells. Blood. 2001;98:3784–92. PubMed

Valent P, Sadovnik I, Eisenwort G, Herrmann H, Bauer K, Mueller N, et al. Redistribution, homing and organ-invasion of neoplastic stem cells in myeloid neoplasms. Semin Cancer Biol. 2020;60:191–201. PubMed PMC

Sotlar K, Cerny-Reiterer S, Petat-Dutter K, Hessel H, Berezowska S, Müllauer L, et al. Aberrant epression of CD30 in neoplastic mast cells in high-grade mastocytosis. Mod Pathol. 2011;24:585–95. PubMed

Valent P, Sotlar K, Horny H-P. Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in aggressive hematopoietic CD30-positive neoplasms. Leuk Lymphoma. 2011;52:740–4. PubMed

Morgado JM, Perbellini O, Johnson RC, Teodósio C, Matito A, Álvarez-Twose I, et al. CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis. Histopathology. 2013;63:780–7. PubMed

Van Anrooij B, Kluin PM, Oude Elberink JNG, Kluin-Nelemans JC. CD30 in systemic mastocytosis. Immunol Allergy Clin North Am. 2014;34:341–55. PubMed

Escribano L, Orfao A, Villarrubia J, Martín F, Madruga JI, Cuevas M, et al. Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia. Cytometry. 1997;30:98–102. PubMed

Valent P, Oude Elberink JNG, Gorska A, Lange M, Zanotti R, van Anrooij B, et al. The Data Registry of the European Competence Network on Mastocytosis (ECNM): Set Up, Projects, and Perspectives. J Allergy Clin Immunol Pr. 2019;7:81–87. PubMed PMC

Valent P, Hartmann K, Bonadonna P, Sperr WR, Niedoszytko M, Hermine O, et al. European Competence Network on Mastocytosis (ECNM): 20-Year Jubilee, Updates, and Future Perspectives. J Allergy Clin Immunol Pr. 2023;11:1706–17. PubMed

Valent P, Cerny-Reiterer S, Herrmann H, Mirkina I, George TI, Sotlar K, et al. Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells. Best Pr Res Clin Haematol. 2010;23:369–78. PubMed

Rossignol J, Georgin-Lavialle S, Canioni D, Beganovic O, Brouzes C, Fain O, et al. Characteristics and outcomes associated with CD2 and CD25 expression on bone marrow mast cells in patients with systemic mastocytosis. Haematologica. 2024. 29. 10.3324/haematol.2024.285740. PubMed PMC

Jawhar M, Schwaab J, Álvarez-Twose I, Shoumariyeh K, Naumann N, Lübke J, et al. MARS: mutation-adjusted risk score for advanced systemic mastocytosis. J Clin Oncol. 2019;37:2846–56. PubMed PMC

Lübke J, Schwaab J, Christen D, Elberink HO, Span B, Niedoszytko M, et al. Prognostic impact of organomegaly in mastocytosis: an analysis of the european competence network on mastocytosis. J Allergy Clin Immunol Pr. 2023;11:581–590.e5. PubMed

Blatt K, Cemy-Reiterer S, Schwaab J, Sotlar K, Eisenwort G, Stefanzl G, et al. Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis. Blood. 2015;126:2832–41. PubMed PMC

Sadovnik I, Hoelbl-Kovacic A, Herrmann H, Eisenwort G, Cerny-Reiterer S, Warsch W, et al. Identification of CD25 as STAT5-dependent growth regulator of leukemic stem cells in Ph+ CML. Clin Cancer Res. 2016;22:2051–61. PubMed PMC