Use of JAG2 expression in diagnosis of plasma cell disorders

• US 7,449,303 B2
• Filed: 05/03/2004
• Issued: 11/11/2008
• Est. Priority Date: 05/02/2003
• Status: Expired due to Fees

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Coignet, Lionel J.
• Primary Examiner(s): Spector; Lorraine
• Assistant Examiner(s): Kaufman; Claire
• Application Number:
  US10/837,722
• Publication Number:
  US 20050003406A1
• Time in Patent Office: 1,653 Days
• Field of Search: None
• US Class Current: 435/7.21
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57426 leukemia

Abstract

The present invention is based on the finding that plasma cell disorders such as Multiple Myeloma and Monoclonal Gammopathy of Unknown Significance are characterized by an increase in the expression of JAG2. Accordingly, the present invention provides a method for diagnosis of plasma cell disorders by detecting the expression or overexpression of JAG2. The expression or overexpression of JAG2 may be detected as increased mRNA transcripts or increased protein.

Claims

1. A method for diagnosis of a plasma cell disorder in an individual comprising detecting in a bone marrow sample comprising plasma cells from the individual, wherein the bone marrow sample is processed to enrich for plasma cells:

a) JAG2 mRNA expression, or

b) JAG2 protein;

wherein overexpression of JAG2 mRNA relative to a normal control, or overexpression of JAG2 protein relative to a normal control is indicative that the individual has a plasma cell disorder selected from the group consisting of monoclonal gammopathy of unknown significance (MGUS), smoldering myeloma, multiple myeloma and plasma cell leukemia.

2. The method of claim 1, wherein detection of JAG2 mRNA is carried out by a method selected from the group consisting of Northern Blotting, in situ hybridization, PCR based techniques, and a combination thereof.

3. The method of claim 2, wherein the PCR based technique is RT-PCR.

4. The method of claim 3, wherein a pair of primers used for RT-PCR has the sequences of SEQ ID NO:

1 and SEQ ID NO;

2.

5. The method of claim 1, wherein detection of JAG2 protein is carried out using polyclonal or monoclonal antibodies, or antigen-binding fragments thereof specific for the JAG2 protein.

6. The method of claim 5, wherein the detection of JAG2 protein is carried out by using FACS analysis using a monoclonal antibody.

7. The method of claim 5, wherein the detection of JAG2 protein is carried out by using a polyclonal antibody.

8. The method of claim 5, wherein the detection of JAG2 protein is carried out by using a monoclonal antibody.

9. The method of claim 5, wherein the monoclonal antibody is specific against the peptide of SEQ ID NO:

3.

10. The method of claim 9, wherein the monoclonal antibody is monoclonal antibody M8.

11. The method of claim 1, wherein the bone marrow sample is enriched in plasma cells by selective adsorption by plasma cell specific antibodies.

12. The method of claim 11, wherein the plasma cell specific antibodies comprise monoclonal antibody M8.

13. The method of claim 1, wherein the level of expression of JAG2 mRNA or the level of JAG protein in the bone marrow sample is compared to a negative control.

14. A method for determining a plasma cell disorder in an individual comprising the step of detecting in a bone marrow sample from the individual comprising plasma cells:

JAG2 protein expression,

wherein expression of JAG2 protein of about 10 times greater than the level of JAG2 protein expression of a normal control is indicative of smoldering myeloma or MGUS, and wherein expression of JAG2 protein of about 100 times greater than the level of JAG2 protein expression of the normal control is indicative of multiple myeloma.

15. The method of claim 14, wherein detection of JAG2 protein is carried out using polyclonal or monoclonal antibodies, or antigen-binding fragments thereof specific for the JAG2 protein.

16. The method of claim 15, wherein the detection of JAG2 protein is carried out by using FACS analysis using a monoclonal antibody.

17. The method of claim 16, wherein the monoclonal antibody is specific for the peptide of SEQ ID NO:

3.

18. A kit for diagnosis of plasma cell disorder in sample comprising plasma cells, said kit comprising a pair of primers which specifically hybridize to a nucleic acid molecule encoding JAG2, and reagents for performing RT-PCR, wherein the sequences of the primer pair are SEQ ID NO:

1 and SEQ ID NO;

2.

19. A kit useful for diagnosis of plasma cell disorder comprising a monoclonal antibody specific for the JAG2 protein, antigen binding fragments of the monoclonal antibody and combinations thereof;

and regents for performing immunological detection, wherein the monoclonal antibody is reactive against the peptide of SEQ ID NO;

3.

20. The kit of claim 19, wherein the monoclonal antibody has a detectable label thereon.

21. The kit of claim 19, wherein the monoclonal antibody is monoclonal antibody is M8.

22. A monoclonal antibody specific for JAG2 protein, wherein the monoclonal antibody thereby binds to plasma cells which express the JAG2 protein on the surface, and wherein the monoclonal antibody is reactive against the peptide of SEQ ID NO:

3.