| Title | Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Cerchietti, Leandro, Damm-Welk Christine, Vater Inga, Klapper Wolfram, Harder Lana, Pott Christiane, Yang Shao Ning, Reiter Alfred, Siebert Reiner, Melnick Ari, and Woessmann Willi |
| Journal | PLoS One |
| Volume | 6 |
| Issue | 4 |
| Pagination | e18436 |
| Date Published | 2011 Apr 08 |
| ISSN | 1932-6203 |
| Keywords | Anaplastic Lymphoma Kinase, Animals, Base Sequence, Cell Death, Cell Line, Tumor, Cell Proliferation, Humans, Immunocompromised Host, Immunophenotyping, Lymphoma, Large B-Cell, Diffuse, Mice, Mice, SCID, Molecular Sequence Data, Oncogene Proteins, Fusion, Protein Kinase Inhibitors, Pyrimidines, Receptor Protein-Tyrosine Kinases, Remission Induction, Signal Transduction, Xenograft Model Antitumor Assays |
| Abstract | <p>ALK positive diffuse large B-cell lymphomas (DLBCL) are a distinct lymphoma subtype associated with a poor outcome. Most of them feature a t(2;17) encoding a clathrin (CLTC)-ALK fusion protein. The contribution of deregulated ALK-activity in the pathogenesis and maintenance of these DLBCLs is not yet known. We established and characterized the first CLTC-ALK positive DLBCL cell line (LM1). LM1 formed tumors in NOD-SCID mice. The selective ALK inhibitor NVP-TAE684 inhibited growth of LM1 cells in vitro at nanomolar concentrations. NVP-TAE684 repressed ALK-activated signalling pathways and induced apoptosis of LM1 DLBCL cells. Inhibition of ALK-activity resulted in sustained tumor regression in the xenotransplant tumor model. These data indicate a role of CLTC-ALK in the maintenance of the malignant phenotype thereby providing a rationale therapeutic target for these otherwise refractory tumors.</p> |
| DOI | 10.1371/journal.pone.0018436 |
| Alternate Journal | PLoS One |
| PubMed ID | 21494621 |
| PubMed Central ID | PMC3072987 |