![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
2MB |
| Item Type: | Article |
|---|---|
| Title: | Aberrant expression of and cell death induction by engagement of the MHC-II chaperone CD74 in anaplastic large cell lymphoma (ALCL) |
| Creators Name: | Wurster, K.D., Costanza, M., Kreher, S., Glaser, S., Lamprecht, B., Schleussner, N., Anagnostopoulos, I., Hummel, M., Jöhrens, K., Stein, H., Molina, A., Diepstra, A., Gillissen, B., Köchert, K., Siebert, R., Merkel, O., Kenner, L., Janz, M. and Mathas, S. |
| Abstract: | In 50-60% of cases, systemic anaplastic large cell lymphoma (ALCL) is characterized by the t(2;5)(p23;q35) or one of its variants, considered to be causative for anaplastic lymphoma kinase (ALK)-positive (ALK(+)) ALCL. Key pathogenic events in ALK-negative (ALK(-)) ALCL are less well defined. We have previously shown that deregulation of oncogenic genes surrounding the chromosomal breakpoints on 2p and 5q is a unifying feature of both ALK(+) and ALK(-) ALCL and predisposes for occurrence of t(2;5). Here, we report that the invariant chain of the MHC-II complex CD74 or li, which is encoded on 5q32, can act as signaling molecule, and whose expression in lymphoid cells is usually restricted to B cells, is aberrantly expressed in T cell-derived ALCL. Accordingly, ALCL shows an altered DNA methylation pattern of the CD74 locus compared to benign T cells. Functionally, CD74 ligation induces cell death of ALCL cells. Furthermore, CD74 engagement enhances the cytotoxic effects of conventional chemotherapeutics in ALCL cell lines, as well as the action of the ALK-inhibitor crizotinib in ALK(+) ALCL or of CD95 death-receptor signaling in ALK(-) ALCL. Additionally, a subset of ALCL cases expresses the proto-oncogene MET, which can form signaling complexes together with CD74. Finally, we demonstrate that the CD74-targeting antibody-drug conjugate STRO-001 efficiently and specifically kills CD74-positive ALCL cell lines in vitro. Taken together, these findings enabled us to demonstrate aberrant CD74-expression in ALCL cells, which might serve as tool for the development of new treatment strategies for this lymphoma entity. |
| Keywords: | CD74, Invariant Chain, MHC-II, T Cell Lymphoma, ALK Translocation |
| Source: | Cancers |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Volume: | 13 |
| Number: | 19 |
| Page Range: | 5012 |
| Date: | 1 October 2021 |
| Official Publication: | https://doi.org/10.3390/cancers13195012 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
