Differential effects of lenalidomide during plasma cell differentiation.
Differential effects of lenalidomide during plasma cell differentiation.
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DOI：
10.18632/oncotarget.8581
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Klein B
中科院分区：
文献类型：
--
作者：
Jourdan M;Cren M;Schafer P;Robert N;Duperray C;Vincent L;Ceballos P;Cartron G;Rossi JF;Moreaux J;Chopra R;Klein B
沙利度胺、来那度胺和泊马度胺极大地改善了多发性骨髓瘤患者的预后。然而，它们对浆细胞的影响尚不清楚，浆细胞是骨髓瘤细胞的健康对应物。在这里，我们使用体外模型研究来那度胺对正常人浆细胞生成的影响。来那度胺抑制前浆母细胞和早期浆细胞的生成，但对浆母细胞的生成有一定的影响。它还降低了Ikaros、Aiolos和IRF4转录因子在浆母细胞和早期浆细胞中的表达水平。这表明它们对来那度胺的差异敏感性不是由于Ikaros或Aiolos降解率的差异。来那度胺也抑制长寿命浆细胞的产生，但一旦产生，不会损害它们的长期存活。最后一个观察结果与来那度胺治疗3-18个月不影响多发性骨髓瘤异基因移植患者骨髓健康浆细胞计数的发现是一致的。我们的发现应该促使我们调查多发性骨髓瘤患者对来那度胺的耐药性是否与恶性浆母细胞或对来那度胺不那么敏感的长寿命浆细胞的出现有关。
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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影响因子：
64.8
作者：
Shaffer, Arthur L.;Emre, N. C. Tolga;Staudt, Louis M.
通讯作者：
Staudt, Louis M.
DOI：
10.3324/haematol.2009.018689
发表时间：
2010-06-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Caraux, Anouk;Klein, Bernard;Perez-Andres, Martin
通讯作者：
Perez-Andres, Martin
影响因子：
20.3
作者：
Barlogie, B;Desikan, R;Tricot, G
通讯作者：
Tricot, G
影响因子：
4.4
作者：
Jourdan, Michel;Caraux, Anouk;Klein, Bernard
通讯作者：
Klein, Bernard
影响因子：
4.4
作者：
Cocco, Mario;Stephenson, Sophie;Tooze, Reuben M.
通讯作者：
Tooze, Reuben M.