Potential Therapeutic Targets in Plasma Cell Disorders: A Flow Cytometry Study

被引:11
作者
Lisenko, Katharina [1 ]
Schoenland, Stefan [1 ]
Hegenbart, Ute [1 ]
Wallenwein, Katrin [1 ]
Braun, Ute [1 ]
Mai, Elias K. [1 ]
Hillengass, Jens [1 ]
Goldschmidt, Hartmut [1 ,2 ]
Jauch, Anna [3 ]
Ho, Anthony D. [1 ]
Raab, Marc [1 ]
Hundemer, Michael [1 ]
机构
[1] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany
[2] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany
[3] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany
关键词
plasma cell disorders; SLAMF7; CD20; immunophenotyping; MULTIPLE-MYELOMA; EXPRESSION; ANTIBODY; CS1; ACTIVATION; CRITERIA; CD30; CD52;
D O I
10.1002/cyto.b.21351
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
The discovery of new targets for tailored therapy is a major improvement in oncology, and tools for the rapid and reliable detection of these targets are essential. Clinical trials demonstrated the benefit of recently developed antibodies against antigens on malignant B-cells. The aim of this study was to assess patients with plasma cell (PC) disorders for expression of antigens on malignant PCs that have exhibited promise in targeted cancer therapy. We retrospectively analyzed the expression of CD20, CD22, CD27, CD30, CD38, CD52, CD81, CD138, and SLAMF7 on PCs by flow cytometry in 103 patients with PC disorders. Furthermore, we studied cytogenetic data to correlate immunophenotyping and genetic parameters. The expression frequency of CD22, CD30, and CD52 was similar to other studies (12-35%, 0-19%, and 0-8%, respectively). Unexpectedly, we observed a high CD20 expression frequency in 37% of all AL-amyloidosis cases. The presence of t(11;14) correlated positively with CD20 expression on PCs in AL-amyloidosis (p=0.018). Furthermore, the expression level of SLAMF7 was decreased in advanced PC disorders (p=0.025) and a diminished expression of SLAMF7 is associated with low expression of CD27 and CD81 on malignant PCs in newly diagnosed multiple myeloma. This study provides a contribution to targeted therapy options in PC disorders. Particularly, the results put an emphasis on CD20 as therapeutic target in AL-amyloidosis. Regarding the therapeutic options of the SLAMF7 antibody elotuzumab, these data advise that analysis of SLAMF7 expression before application of elotuzumab might help to estimate the efficacy of elotuzumab in clinical trials. (C) 2015 International Clinical Cytometry Society
引用
收藏
页码:145 / 152
页数:8
相关论文
共 45 条
  • [1] t(11;14) multiple myeloma: A subtype associated with distinct immunological features, immunophenotypic characteristics but divergent outcome
    An, Gang
    Xu, Yan
    Shi, Lihui
    Zou, Dehui
    Deng, Shuhui
    Sui, Weiwei
    Xie, Zhenqing
    Hao, Mu
    Chang, Hong
    Qiu, Lugui
    [J]. LEUKEMIA RESEARCH, 2013, 37 (10) : 1251 - 1257
  • [2] Arroz M, 2015, CYTOMETRY B
  • [3] Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-α pathways
    Balasa, Balaji
    Yun, Rui
    Belmar, Nicole A.
    Fox, Melvin
    Chao, Debra T.
    Robbins, Michael D.
    Starling, Gary C.
    Rice, Audie G.
    [J]. CANCER IMMUNOLOGY IMMUNOTHERAPY, 2015, 64 (01) : 61 - 73
  • [4] Hyperdiploidy is less frequent in AL amyloidosis compared with monoclonal gammopathy of undetermined significance and inversely associated with translocation t(11;14)
    Bochtler, Tilmann
    Hegenbart, Ute
    Heiss, Christiane
    Benner, Axel
    Moos, Marion
    Seckinger, Anja
    Pschowski-Zuck, Stephanie
    Kirn, Desiree
    Neben, Kai
    Bartram, Claus R.
    Ho, Anthony D.
    Goldschmidt, Hartmut
    Hose, Dirk
    Jauch, Anna
    Schonland, Stefan O.
    [J]. BLOOD, 2011, 117 (14) : 3809 - 3815
  • [5] Brentuximab vedotin: An anti-CD30 antibody-drug conjugate
    Bradley, Amber M.
    Devine, Meghan
    DeRemer, David
    [J]. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 2013, 70 (07) : 589 - 597
  • [6] CD52 antigen expressed by malignant plasma cells can be targeted by alerntuzumab in vivo in NOD/SCID mice
    Carlo-Stella, Carmelo
    Guidetti, Anna
    Di Nicola, Massimo
    Longoni, Paolo
    Cleris, Loredana
    Lavazza, Cristiana
    Milanesi, Marco
    Milani, Raffaella
    Carrabba, Matteo
    Farina, Lucia
    Formelli, Franca
    Gianni, Alessandro M.
    Corradini, Paolo
    [J]. EXPERIMENTAL HEMATOLOGY, 2006, 34 (06) : 721 - 727
  • [7] Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab
    Carnahan, Josette
    Stein, Rhona
    Qu, Zhengxing
    Hess, Kristen
    Cesano, Alessandra
    Hansen, Hans J.
    Goldenberg, David M.
    [J]. MOLECULAR IMMUNOLOGY, 2007, 44 (06) : 1331 - 1341
  • [8] Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC
    Collins, Shauna M.
    Bakan, Courtney E.
    Swartzel, Gina D.
    Hofmeister, Craig C.
    Efebera, Yvonne A.
    Kwon, Hakju
    Starling, Gary C.
    Ciarlariello, David
    Bhaskar, Shakthi
    Briercheck, Edward L.
    Hughes, Tiffany
    Yu, Jianhua
    Rice, Audie
    Benson, Don M., Jr.
    [J]. CANCER IMMUNOLOGY IMMUNOTHERAPY, 2013, 62 (12) : 1841 - 1849
  • [9] Immunophenotype of neoplastic plasma cells in AL amyloidosis
    Deshmukh, M.
    Elderfield, K.
    Rahemtulla, A.
    Naresh, K. N.
    [J]. JOURNAL OF CLINICAL PATHOLOGY, 2009, 62 (08) : 724 - 730
  • [10] International uniform response criteria for multiple myeloma
    Durie, B. G. M.
    Harousseau, J-L
    Miguel, J. S.
    Blade, J.
    Barlogie, B.
    Anderson, K.
    Gertz, M.
    Dimopoulos, M.
    Westin, J.
    Sonneveld, P.
    Ludwig, H.
    Gahrton, G.
    Beksac, M.
    Crowley, J.
    Belch, A.
    Boccadaro, M.
    Turesson, I.
    Joshua, D.
    Vesole, D.
    Kyle, R.
    Alexanian, R.
    Tricot, G.
    Attal, M.
    Merlini, G.
    Powles, R.
    Richardson, P.
    Shimizu, K.
    Tosi, P.
    Morgan, G.
    Rajkumar, S. V.
    [J]. LEUKEMIA, 2006, 20 (09) : 1467 - 1473