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  • Original Article
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Chronic myleproliferative neoplasms

CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value

Leukemia volume 30, pages 914–918 (2016)Cite this article

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Abstract

CD123 is the α-subunit of the interleukin-3 receptor; it represents a potential therapeutic target in systemic mastocytosis (SM) given its absent expression on normal/reactive mast cells (MCs) and aberrant expression on neoplastic MCs. We studied 58 SM patients to define CD123 expression patterns by immunohistochemistry and its clinical significance. Two hematopathologists independently scored bone marrow slides using predefined histologic parameters. In all, 23 patients had indolent SM (ISM), 10 aggressive SM (ASM), 23 SM with associated hematological neoplasm (SM-AHN) and 2 had mast cell leukemia (MCL). MC_CD123 expression was demonstrable in 37 (64%) cases; expression rates were 100%, 61%, 57% and 0% in ASM, ISM, SM-AHN and MCL, respectively (P=0.02). Focal proliferation of plasmacytoid dendritic cells (PDCs) around MC aggregates, suggesting a tumor-promoting role for PDCs, was noted in 44 (76%) cases, and was significantly higher in CD123-positive versus -negative cases (87% versus 50%, P=0.005). CD123 expression and its staining intensity had prognostic value in SM-chronic myelomonocytic leukemia and nonindolent SM patients, respectively. These observations suggest that targeting CD123 in SM may have direct (via MCs) and indirect (via PDCs) antitumor effects and clinical trials to that effect require laboratory correlative studies to address the observed target expression heterogeneity.

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References

  1. Woodcock JM, Bagley CJ, Zacharakis B, Lopez AF . A single tyrosine residue in the membrane-proximal domain of the granulocyte-macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 receptor common beta-chain is necessary and sufficient for high affinity binding and signaling by all three ligands. J Biol Chem 1996; 271: 25999–26006.

    Article  CAS  Google Scholar 

  2. Testa U, Fossati C, Samoggia P, Masciulli R, Mariani G, Hassan HJ et al. Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors. Blood 1996; 88: 3391–3406.

    CAS  Google Scholar 

  3. Militi S, Riccioni R, Parolini I, Sposi NM, Samoggia P, Pelosi E et al. Expression of interleukin 3 and granulocyte-macrophage colony-stimulating factor receptor common chain betac, betaIT in normal haematopoiesis: lineage specificity and proliferation-independent induction. Br J Haematol 2000; 111: 441–451.

    Article  CAS  Google Scholar 

  4. Reichard KK, Burks EJ, Foucar MK, Wilson CS, Viswanatha DS, Hozier JC et al. CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells. Am J Surg Pathol 2005; 29: 1274–1283.

    Article  Google Scholar 

  5. Testa U, Pelosi E, Frankel A . CD 123 is a membrane biomarker and a therapeutic target in hematologic malignancies. Biomark Res 2014; 2: 4.

    Article  Google Scholar 

  6. Valent P, Besemer J, Sillaber C, Butterfield JH, Eher R, Majdic O et al. Failure to detect IL-3-binding sites on human mast cells. J Immunol 1990; 145: 3432–3437.

    CAS  Google Scholar 

  7. Pardanani A, Lasho T, Chen D, Kimlinger TK, Finke C, Zblewski D et al. Aberrant expression of CD123 (interleukin-3 receptor-alpha) on neoplastic mast cells. Leukemia 2015; 29: 1605–1608.

    Article  CAS  Google Scholar 

  8. Horny HP, Metcalfe DD, Bennett JM, Bain BJ, Akin C, Escribano L et al Mastocytosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4th edn. International Agency for Research and Cancer (IARC): Lyon, 2008; pp 54–63.

    Google Scholar 

  9. Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C . Interleukin-3 receptor in acute leukemia. Leukemia 2004; 18: 219–226.

    Article  CAS  Google Scholar 

  10. Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P et al. Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood 2002; 100: 2980–2988.

    Article  CAS  Google Scholar 

  11. De Waele M, Renmans W, Vander Gucht K, Jochmans K, Schots R, Otten J et al. Growth factor receptor profile of CD34+ cells in AML and B-lineage ALL and in their normal bone marrow counterparts. Eur J Haematol 2001; 66: 178–187.

    Article  CAS  Google Scholar 

  12. Chauhan D, Singh AV, Brahmandam M, Carrasco R, Bandi M, Hideshima T et al. Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell 2009; 16: 309–323.

    Article  CAS  Google Scholar 

  13. Chen YC, Chou JM, Ketterling RP, Letendre L, Li CY . Histologic and immunohistochemical study of bone marrow monocytic nodules in 21 cases with myelodysplasia. Am J Clin Pathol 2003; 120: 874–881.

    Article  Google Scholar 

  14. Vermi W, Facchetti F, Rosati S, Vergoni F, Rossi E, Festa S et al. Nodal and extranodal tumor-forming accumulation of plasmacytoid monocytes/interferon-producing cells associated with myeloid disorders. Am J Surg Pathol 2004; 28: 585–595.

    Article  Google Scholar 

  15. Ray A, Das DS, Song Y, Richardson P, Munshi NC, Chauhan D et al. Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells, natural killer cells and multiple myeloma cells. Leukemia 2015; 29: 1441–1444.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was funded by a grant from the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Author contributions

AP, KKR and DC designed the project and analyzed the data. KKR and DC performed the primary blinded review of bone marrow slides with scoring of predefined histological parameters. CAH, KLG and WGM provided additional hematopathology review. DZ, RAA and EAW abstracted clinical data from patient medical charts. AT and CB assisted in scientific review and data analysis. AP wrote the first draft of the paper. All the authors reviewed the manuscript draft, provided critical input and approved the final version of the manuscript. AP and DC had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    A Pardanani, D Zblewski, R A Abdelrahman, E A Wassie & A Tefferi

  2. Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    K K Reichard, W G Morice II, K L Grogg, C A Hanson & D Chen

  3. Stemline Therapeutics Inc., New York, NY, USA

    C Brooks

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  1. A Pardanani
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  2. K K Reichard
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Corresponding author

Correspondence to A Pardanani.

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Competing interests

AP received a research grant from Stemline therapeutics for preclinical study of the CD123-targeting drug, SL-701. CB is an employee of Stemline Therapeutics.

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Supplementary Information accompanies this paper on the Leukemia website

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Pardanani, A., Reichard, K., Zblewski, D. et al. CD123 immunostaining patterns in systemic mastocytosis: differential expression in disease subgroups and potential prognostic value. Leukemia 30, 914–918 (2016). https://doi.org/10.1038/leu.2015.348

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