title: Differential effects of lenalidomide during plasma cell differentiation.
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.
authors.affiliation: INSERM, U1040, Montpellier, France.|CNRS UPR1142, Institute of Human Genetics, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Jourdan
authors.affiliation: INSERM, U1040, Montpellier, France.
authors.forename: Maïlys
authors.initials: M
authors.lastname: Cren
authors.affiliation: Translational Development Department, Celgene Corporation, Summit, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Schafer
authors.affiliation: CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Hematology, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Robert
authors.affiliation: Cytometry IRB, Montpellier Rio Imaging, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duperray
authors.affiliation: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Vincent
authors.affiliation: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Ceballos
authors.affiliation: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.|University Montpellier 1, UFR Medicine, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.affiliation: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.|University Montpellier 1, UFR Medicine, Montpellier, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossi
authors.affiliation: CNRS UPR1142, Institute of Human Genetics, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Hematology, Montpellier, France.|University Montpellier 1, UFR Medicine, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.affiliation: Translational Development Department, Celgene Corporation, Summit, NJ, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
authors.affiliation: CNRS UPR1142, Institute of Human Genetics, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Hematology, Montpellier, France.|University Montpellier 1, UFR Medicine, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018365:Neoplasm, Residual / Q000188:drug therapy; D010950:Plasma Cells / Q000187:drug effects*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide
keywords: IKZF1; IKZF3; differentiation; lenalidomide; plasma cell