Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis.

Abstract

Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders characterized by refractory cytopenias and susceptibility to leukemic transformation. On a subset of MDS patients with deletion of the long arm of chromosome 5 (del(5q)), lenalidomide exerts hematological and cytogenetic effects, but the underlying pharmacological mechanisms are not fully understood. In this study, we have investigated the in vitro effects of lenalidomide on an MDS-derived cell line, MDS-L, which carries del(5q) and complex chromosome abnormalities. We found that the growth of MDS-L cells was specifically suppressed mainly by apoptosis, and in addition, multinucleated cells were frequently formed and finally died out in the presence of lenalidomide. Time-lapse microscopic observation and the DNA ploidy analysis revealed that lenalidomide does not affect DNA synthesis but inhibits cytokinesis of MDS-L cells. The gene expression profile showed decreased expression of M phase-related genes such as non-muscle myosin heavy-chain 10, polo-like kinase 1, aurora kinase B, citron kinase and kinesin family member 20A(KIF20A). Interestingly, KIF20A is located at 5q31. These data contribute to the understanding of action mechanisms of lenalidomide on MDS with del(5q) and complex abnormalities.

• Authors: A Matsuoka, A Tochigi, M Kishimoto, T Nakahara, T Kondo, T Tsujioka, T Tasaka, Y Tohyama, K Tohyama
• Journal: Leukemia (Leukemia) Vol. 24 Issue 4 Pg. 748-55 (Apr 2010) ISSN: 1476-5551 [Electronic] England
• PMID: 20130600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• RNA, Messenger
• Thalidomide
• Lenalidomide

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Cell Division (drug effects)
• Cell Proliferation (drug effects)
• Chromosome Deletion
• Chromosomes, Human, Pair 5 (genetics)
• Cytokinesis (drug effects)
• Fluorescent Antibody Technique
• Gene Expression Profiling
• Humans
• Karyotyping
• Lenalidomide
• Myelodysplastic Syndromes (drug therapy, genetics, pathology)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Thalidomide (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured