Oncotarget

Research Papers:

Differential effects of lenalidomide during plasma cell differentiation

Michel Jourdan, Maïlys Cren, Peter Schafer, Nicolas Robert, Christophe Duperray, Laure Vincent, Patrice Ceballos, Guillaume Cartron, Jean-François Rossi, Jérôme Moreaux _, Rajesh Chopra and Bernard Klein

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Oncotarget. 2016; 7:28096-28111. https://doi.org/10.18632/oncotarget.8581

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Abstract

Michel Jourdan1,2, Maïlys Cren1, Peter Schafer3, Nicolas Robert4, Christophe Duperray5, Laure Vincent6, Patrice Ceballos6, Guillaume Cartron6,7, Jean-François Rossi6,7, Jérôme Moreaux2,4,7, Rajesh Chopra3, Bernard Klein2,4,7

1INSERM, U1040, Montpellier, France

2CNRS UPR1142, Institute of Human Genetics, Montpellier, France

3Translational Development Department, Celgene Corporation, Summit, NJ, USA

4CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Hematology, Montpellier, France

5Cytometry IRB, Montpellier Rio Imaging, Montpellier, France

6CHU Montpellier, Department of Clinical Hematology, Montpellier, France

7University Montpellier 1, UFR Medicine, Montpellier, France

Correspondence to:

Jérôme Moreaux, email: [email protected]

Keywords: plasma cell, differentiation, IKZF1, IKZF3, lenalidomide

Received: February 05, 2016     Accepted: March 28, 2016     Published: April 4, 2016

ABSTRACT

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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