Description of Invention:
CCAAT/enhancer binding protein alpha (C/EBPalpha) is a leucine-zipper structure transcription factor that plays a key role in regulating the differentiation and proliferation of a variety of cell types. For example, conditional expression of C/EBPalpha is sufficient to trigger neutrophilic differentiation. In addition, administration of antisense molecules against C/EBPalpha has been shown to interfere with proliferation of the late myeloblast and promyelocytic leukemic cell lines HL60 and NB4.
Dominant negative mutations of the CEBPA gene have been identified in a large percentage of subjects with t(8;21) acute myeloid leukemia (AML), subtypes M1 and M2. AML is a cancer of the blood and bone marrow characterized by rapid and uncontrolled growth of myelocytes and a lack of myeloid cell differentiation. Approximately 8% of all AML cases are of the t(8;21) variety. Therefore, pharmacologic modulators of C/EBPalpha may be useful as a means to induce cell differentiation, and thus limit proliferation of AML cells.
The present invention describes methods for treating various leukemic disorders by administrating compounds. Additional embodiments describe the mechanism of action of these sterol mesylate compounds through their ability to modulate C/EBPalpha. This disclosure also provides methods for screening for C/EBPalpha inducing compounds. Sterol mesylate compounds and derivatives thereof have the potential to result in more effective therapeutics for the treatment of leukemia and lymphoma.
Inventors:
Robert H. Shoemaker (NCI) et al.
Patent Status:
DHHS Reference No. E-140-2005/0-US-01 -- U.S. Provisional Application No. 60/699,971 filed 15 Jul 2005 Licensing Status:
In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Cancer
Cancer -Therapeutics-Biological Response Modifiers-Other Cancer -Therapeutics
For Additional Information Please Contact: Michelle A. Booden Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)451-7337
Email: boodenm@mail.nih.gov
Fax: (301) 402-0220
