Claims
- 1. A method of degrading BCL-6 in cells comprising:
administering a molecule which induces phosphorylation of BCL-6 and thereby induces BCL-6 degradation.
- 2. The method of claim 1 wherein the molecule which induces phosphorylation of the BCL-6 is a mitogen-activated protein kinase (MAPK).
- 3. The method of claim 1 wherein the molecule which induces phosphorylation of the BCL-6 is a functionally active mutant of a mitogen-activated protein kinase (MAPK).
- 4. The method of claim 2 wherein the MAPK is ERK-1 or ERK-2.
- 5. The method of claim 1, wherein the BCL-6 is phosphorylated either at one site or at multiple sites.
- 6. The method of claim 1, wherein the molecule which induces phosphorylation of the BCL-6 is a molecule which activates an antigen receptor on B cell surfaces.
- 7. The method of claim 6, wherein the molecule which activates an antigen receptor on B cell surfaces is an antibody.
- 8. The method of claim 7, wherein the antibody is an anti-IgM antibody.
- 9. The method of claim 6, wherein the molecule which activates an antigen receptor on B cell surfaces is a molecule which activates MAPK in B cells.
- 10. The method of claim 9, wherein the molecule which activates MAPK in B cells is a cytokine.
- 11. The method of claim 10, wherein the cytokine is TNF, IL-6, or IL-2.
- 12. The method of claim 1, wherein the molecule is cross-linked to a B cell antigen receptor to activate the receptor.
- 13. The method of claim 1, wherein cross-linking the molecule to the B cell antigen receptor activates the MAPK.
- 14. A method of treating a subject with lymphoma which comprises:
administering an effective amount of a pharmaceutical composition comprising a molecule which induces phosphorylation of BCL-6 protein so as to induce degradation of BCL-6 and a pharmaceutically acceptable carrier, thereby treating the subject with lymphoma.
- 15. The method of claim 14, wherein the lymphoma expresses BCL-6.
- 16. The method of claim 14, wherein the pharmaceutical composition comprises a MAPK activator.
- 17. The method of claim 16, wherein the MAPK activator is an antibody.
- 18. The method of claim 17, wherein the antibody is an anti-IgM antibody.
- 19. The method of claim 16, wherein the MAPK activator is a cytokine.
- 20. The method of claim 19, wherein the cytokine is TNF, IL-6, or IL-2.
- 21. The method of claim 14, wherein the lymphoma is a B-cell lymphoma.
- 22. The method of claim 21, wherein the B-cell lymphoma is derived from germinal center B cells.
- 23. The method of claim 14, wherein the administration of the pharmaceutical composition is intravenous or intratumor.
- 24. A method of regulating deceasing BCL-6 levels in cells comprising administering a compound which interferes with transcription of bcl-6 and thereby prevents expression of BCL-6 protein so as to thereby deceasing BCL-6 levels in the cells.
- 25. The method of claim 24, wherein the compound which interferes with transcription of bcl-6 prevents binding of a transcription factor and histone acetylase/deacetylase complexes.
- 26. The method of claim 25, wherein the compound is N,N′-hexamethylene bisacetamide (HMBA) or trichostatin.
- 27. A method of treating lymphoma comprising decreasing BCL-6 levels in cells comprising the method of claim 24.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US94/06669 |
Jun 1994 |
US |
|
Parent Case Info
[0001] This application is a continuation-in-part of U.S. application Ser. No. 08/074,967, filed on Jun. 9, 1993, the contents of which are hereby incorporated by reference.
Government Interests
[0002] The invention disclosed herein was made with Government support under NIH Grant Nos. CA-44029, CA-34775, CA-08748 and CA-37295 from the Department of Health and Human Services. Accordingly, the U.S. Government has certain rights in this invention.