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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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September 2012 Volume 41 Issue 3

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Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide

  • Authors:
    • Yawara Kawano
    • Shiho Fujiwara
    • Naoko Wada
    • Mikiko Izaki
    • Hiromichi Yuki
    • Yutaka Okuno
    • Kenichi Iyama
    • Hiroshi Yamasaki
    • Akira Sakai
    • Hiroaki Mitsuya
    • Hiroyuki Hata
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan, Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto, Japan, Department of Hematology and Oncology, Kumamoto City Hospital, Kumamoto, Japan, Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan, Department of Hematology, Faculty of Life Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto, Japan
    Copyright: © Kawano et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 876-884
    |
    Published online on: July 4, 2012
       https://doi.org/10.3892/ijo.2012.1545
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Abstract

CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patients with relapsed/progressive disease compared with untreated MM patients. Patients with low levels of CD138 had a worse overall survival compared with patients with high levels of CD138, in newly diagnosed patients and patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation. Two MM cell lines, KYMM-1 (CD138- low) and KYMM-2 (CD138- high), were established from a single MM patient with decreased CD138 expression. High expression of BCL6 and PAX5, and downregulation of IRF4, PRDM1 and XBP1 was observed in KYMM-1 compared with KYMM-2 cells, indicative of the immature phenotype of KYMM-1. KYMM-1 was less sensitive to lenalidomide than KYMM-2, while no difference in sensitivity to bortezomib was observed. KYMM-2 cells were further divided in CD138+ and CD138- fractions using anti-CD138-coated magnetic beads. CD138- cells sorted from the KYMM-2 cell line also showed high BCL6, low IRF4 expression and decreased sensitivity to lenalidomide compared with CD138+ cells. Our observations suggest that low CD138 expression relates to i) poor prognosis, ii) immature phenotype and iii) low sensitivity to lenalidomide. The observed distinct characteristics of CD138 low MM cells, suggest this should be recognized as a new clinical entity. Establishment of a treatment strategy for MM cells expressing low levels of CD138 is needed to improve their poor outcome.
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Copy and paste a formatted citation
Spandidos Publications style
Kawano Y, Fujiwara S, Wada N, Izaki M, Yuki H, Okuno Y, Iyama K, Yamasaki H, Sakai A, Mitsuya H, Mitsuya H, et al: Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol 41: 876-884, 2012.
APA
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y. ... Hata, H. (2012). Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. International Journal of Oncology, 41, 876-884. https://doi.org/10.3892/ijo.2012.1545
MLA
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., Hata, H."Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide". International Journal of Oncology 41.3 (2012): 876-884.
Chicago
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., Hata, H."Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide". International Journal of Oncology 41, no. 3 (2012): 876-884. https://doi.org/10.3892/ijo.2012.1545
Copy and paste a formatted citation
x
Spandidos Publications style
Kawano Y, Fujiwara S, Wada N, Izaki M, Yuki H, Okuno Y, Iyama K, Yamasaki H, Sakai A, Mitsuya H, Mitsuya H, et al: Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol 41: 876-884, 2012.
APA
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y. ... Hata, H. (2012). Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. International Journal of Oncology, 41, 876-884. https://doi.org/10.3892/ijo.2012.1545
MLA
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., Hata, H."Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide". International Journal of Oncology 41.3 (2012): 876-884.
Chicago
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., Hata, H."Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide". International Journal of Oncology 41, no. 3 (2012): 876-884. https://doi.org/10.3892/ijo.2012.1545
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