Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656.

Abstract

We show that prolonged exposure of non-Hodgkin's lymphoma (NHL) cell lines to low doses of the Src family protein tyrosine kinases (SFKs) inhibitor SU6656 caused proliferation abrogation as a result of the formation of cells with single multilobed nuclei and several mitotic spindle poles, features similar to polyploid megakaryocytes. The propensity of the NHL B cells tested to undergo polyploid was unrelated to the presence of p53 mutations in these cells since comparable outcomes were observed in SU6656-exposed cultures of blood B lymphocytes derived from healthy individuals. Thus, in addition to its utility for the study of megakaryocyte polyploidization, our results show that SU6656 can also induce polyploidy in cells of lymphoid origin, revealing a chemotherapeutic potential for this inhibitor to limit tumor propagation of malignant B cell lymphomas, although not without affecting normal B cells as well.

• Authors: Nathalie Dussault, Carl Simard, Sonia Néron, Serge Côté
• Journal: Blood cells, molecules & diseases (Blood Cells Mol Dis) 2007 Jul-Aug Vol. 39 Issue 1 Pg. 130-4 ISSN: 1079-9796 [Print] United States
• PMID: 17434768 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Protein Kinase Inhibitors
• SU 6656
• Sulfonamides

Topics

• B-Lymphocytes (metabolism, pathology)
• Cell Line, Tumor
• Cell Nucleus (metabolism, pathology)
• Drug Screening Assays, Antitumor
• Humans
• Indoles (pharmacology, therapeutic use)
• Lymphoma, B-Cell (drug therapy, metabolism, pathology)
• Megakaryocytes (metabolism, pathology)
• Polyploidy
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Spindle Apparatus (metabolism, pathology)
• Sulfonamides (pharmacology, therapeutic use)