Open Access

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

  • Published online on: July 4, 2012     https://doi.org/10.3892/ijo.2012.1545
  • Pages: 876-884
  • Copyright: © Kawano et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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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September 2012
Volume 41 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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