Differential effects of lenalidomide during plasma cell differentiation.
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Date
2016-05-10ICR Author
Author
Jourdan, M
Cren, M
Schafer, P
Robert, N
Duperray, C
Vincent, L
Ceballos, P
Cartron, G
Rossi, J-F
Moreaux, J
Chopra, R
Klein, B
Type
Journal Article
Metadata
Show full item recordAbstract
Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma. Our findings should prompt to investigate whether lenalidomide resistance in patients with multiple myeloma could be associated with the emergence of malignant plasmablasts or long-lived plasma cells that are less sensitive to lenalidomide.
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Subject
Plasma Cells
Cells, Cultured
Humans
Multiple Myeloma
Neoplasm, Residual
Thalidomide
Antineoplastic Agents
Hematopoietic Stem Cell Transplantation
Cell Differentiation
Lenalidomide
Language
eng
Date accepted
2016-03-28
License start date
2016-05
Citation
Oncotarget, 2016, 7 (19), pp. 28096 - 28111
Publisher
IMPACT JOURNALS LLC