IP Library › Granted Patent US 8,524,467
Granted Patent B2
US 8,524,467 · App. 12/161,482 · Granted Sep 3, 2013

Diagnostic and therapeutic targets for leukemia

Inventors: Yi Zhang (Chapel Hill, NC); Yuki Okada (Carrboro, NC)
Assignee: The University of North Carolina at Chapel Hill
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Quick Facts
Patent No.
US 8,524,467
App. No.
12/161,482
Granted
Sep 3, 2013
Kind
B2
Abstract

The present invention relates to methods of identifying candidate compounds for the treatment of leukemia and diagnostic methods based on histone methylation and HoxA5 promoter activity.

Claims (16)

1. A method of identifying a candidate compound for the prevention and/or treatment of leukemia, the method comprising:

contacting a DOT1L polypeptide with a CALM-AF10 fusion protein in the presence of a test compound under conditions sufficient for binding of the DOT1L polypeptide to the CALM-AF10 fusion protein; and

detecting interaction between the DOT1L polypeptide and the CALM-AF10 fusion protein,

wherein a reduction in interaction between the DOT1L polypeptide and the CALM-AF10 fusion protein in the presence of the test compound as compared with the level of interaction in the absence of the test compound indicates that the test compound is a candidate compound for the treatment of leukemia.

2. The method of claim 1 , wherein DOT1L polypeptide interaction with the CALM-AF10 fusion protein is evaluated by determining binding between the DOT1L polypeptide and CALM-AF10.

3. The method of claim 1 , wherein DOT1L polypeptide interaction with the CALM-AF10 fusion protein is evaluated by determining nuclear localization of CALM-AF10.

4. The method of claim 1 , wherein DOT1L polypeptide interaction with the CALM-AF10 fusion protein is evaluated by determining histone H3 lysine 79 (H3-K79) methylation of HoxA5.

5. The method of claim 4 , wherein the H3-K79 methylation of the HoxA5 promoter is determined.

6. The method of claim 1 , wherein DOT1L polypeptide interaction with the CALM-AF10 fusion protein is evaluated by determining HoxA5 promoter activity.

7. The method of claim 6 , wherein the HoxA5 promoter is operably associated with a heterologous nucleic acid encoding a reporter molecule, and the reporter molecule is detected.

8. The method of claim 7 , wherein the reporter molecule is a polypeptide.

9. The method of claim 8 , wherein the polypeptide is an enzyme.

10. The method of claim 1 , wherein the DOT1L polypeptide and/or CALM-AF10 fusion protein is expressed from a nucleic acid.

11. The method of claim 1 , wherein the leukemia is T cell acute lymphoid leukemia (T-ALL) or acute myeloid leukemia subtype M0/1 (AML-M0/1).

12. The method of claim 1 , wherein the DOT1L polypeptide is a mammalian DOT1L polypeptide and the CALM-AF10 fusion protein is a mammalian CALM-AF10 fusion protein.

13. The method of claim 12 , wherein the DOT1L polypeptide is a human DOT1L polypeptide and the CALM-AF10 fusion protein is a human CALM-AF10 fusion protein.

Assignments (3)
CONFIRMATORY LICENSE Recorded Nov 25, 2009
From: UNIVERSITY OF NORTH CAROLINA CHAPEL HIL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 023568/0210 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2008
From: OKADA, YUKI
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 021783/0475 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2008
From: YI ZHANG, PH.D., FOR HIMSELF AND AS AGENT FOR THE HOWARD HUGHES MEDICAL INSTITUTE
To: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
Reel/Frame 021783/0508 →
Continuity (2)
Provisional Application 60760709 · Jan 20, 2006
Related Publication 20090061443A1 · Mar 5, 2009