# US 9,435,809 B2 · Method of treating and reducing the risk of acute myelogenous leukemia

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- Number: US 9,435,809 B2
- Document ID: US9435809B2
- Status: Granted
- Kind: B2
- Application number: 14/232,801
- Filed: 2012-07-13
- Published: 2014-11-27
- Granted: 2016-09-06
- Earliest claimed: 2011-07-14
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Stephen D. Nimer; Lan Wang
- Inventors: Stephen D. Nimer; Lan Wang
- Web page: https://patentgrep.com/patent/US9435809B2

## CPC

- G01N 33/57505: of the blood, e.g. leukaemia
- C07K 16/18: against material from animals or humans
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5011: {for testing antineoplastic activity}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/40: characterized by post-translational modification
- C12N 2310/14: interfering nucleic acids [NA]
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/158: Expression markers
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2440/10: acylation, e.g. acetylation, formylation, lipoylation, myristoylation, palmitoylation
- G01N 2500/00: Screening for compounds of potential therapeutic value
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention relates to methods and compositions for treating and reducing the risk of Acute Myelogenous Leukemia (AML). In particular, the invention provides methods for identifying novel treatments for AML based on reproducible and detectable changes in AML1-ETO acetylation. The present invention further provides methods of using these treatments.

## Claims

### Claim 1

A method of identifying agents for treating or reducing risk for acute myelogenous leukemia comprising:
providing a system comprising at least AML1-ETO and p300, in which AML1-ETO acetylation level is determinable;
contacting the system with a test agent;
determining AML1-ETO acetylation level when the test agent is present;
comparing the determined AML1-ETO acetylation level with a reference AML1-ETO acetylation level so that any difference between the reference level and the determined level is detected; and
characterizing the test agent's usefulness in treating or reducing risk for acute myelogenous leukemia based on the detected difference.

### Claim 2 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions lacking the test agent.

### Claim 3 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in the system under otherwise identical conditions lacking the test agent.

### Claim 4 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions that include presence of a positive control agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions that include presence of a negative control agent.

### Claim 6 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions lacking the test agent.

### Claim 7 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in a comparable system under otherwise identical conditions lacking the test agent.

### Claim 8 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions that include presence of a positive control agent.

### Claim 9 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions that include presence of a negative control agent.

### Claim 10 (depends on 1)

The method of claim 1, wherein the reference AML1-ETO acetylation level is a historical level.

### Claim 11 (depends on 1)

The method of claim 1, wherein the system is an in vitro system.

### Claim 12 (depends on 11)

The method of claim 11 wherein the in vitro system comprises cultured cells.

### Claim 13 (depends on 12)

The method of claim 12 wherein the cultured cells comprise acute myelogenous leukemia cells.

### Claim 14 (depends on 12)

The method of claim 12 wherein the cultured cells are transfected with a vector containing no insert or the vector containing AML1-ETO (SEQ ID NO.1).

### Claim 15 (depends on 1)

The method of claim 1, wherein the system is an in vivo system.

### Claim 16 (depends on 15)

The method of claim 15 wherein the in vivo system comprises mice expressing AML1-ETO (SEQ ID NO. 1).

### Claim 17 (depends on 1)

The method of claim 1, wherein the acetylation level of AML1-ETO comprises acetylation on amino acid K43.
