Use of JAG2 expression in diagnosis of plasma cell disorders

• US 20050003406A1
• Filed: 05/03/2004
• Published: 01/06/2005
• Est. Priority Date: 05/02/2003
• Status: Active Grant

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Coignet, Lionel J.
• Granted Patent: US 7,449,303 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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:

a) JAG2 mRNA expression, or

b) JAG2 protein;

wherein expression of JAG2 mRNA or the presence of JAG2 protein is indicative of a plasma cell disorder and lack of expression of JAG2 mRNA or absence of JAG2 protein expression is indicative of a disorder other than a plasma cell disorder.

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 1, wherein the bone marrow sample is enriched in plasma cells prior to detection of JAG2 mRNA expression or JAG2 protein.

11. The method of claim 10, 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 are selected from the group consisting of CD138 and CD38.

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 the severity of plasma cell disorder in an individual comprising the step of detecting in a bone marrow sample from the individual comprising plasma cells:

a) JAG2 mRNA expression, or

b) JAG2 protein;

wherein level of expression of JAG2 mRNA or the level of JAG2 protein is indicative of a plasma cell disorder condition selected from the group consisting of MGUS, smoldering myeloma, multiple myeloma and plasma cell leukemia.

15. The method of claim 14, wherein detection of JAG2 mRNA expression is carried out by a method selected from the group consisting of Northern Blotting, in situ hybridization, PCR based techniques, and a combination thereof.

16. The method of claim 15, wherein the PCR based technique is RT-PCR.

17. The method of claim 16, wherein a pair of primers used for RT-PCR have the sequences of SEQ ID NO:

1 and SEQ ID NO;

2.

18. 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.

19. The method of claim 18, wherein the detection of JAG2 protein is carried out by using FACS analysis using a monoclonal antibody.

20. The method of claim 19, wherein the monoclonal antibody is specific for the peptide of SEQ ID NO:

3.

21. A kit for diagnosis of plasma cell disorder in sample comprising plasma cells, said kit comprising one or more pairs of primers which specifically hybridize to a nucleic acid molecule encoding JAG2, and reagents for performing RT-PCR.

22. The kit of claim 21, wherein the sequences of the primer pair are SEQ ID NO:

1 and SEQ ID NO;

2.

23. A kit useful for diagnosis of plasma cell disorder comprising antibodies selected from the group consisting of a monoclonal antibody specific for the JAG2 protein, antigen binding fragments of the monoclonal antibody and combinations thereof;

and regents for performing immunological detection.

24. The kit of claim 23, wherein the monoclonal antibody is specific for the peptide of SEQ ID NO:

3.

25. The kit of claim 23, wherein the monoclonal antibody has a detectable label thereon.

26. A monoclonal antibody specific for JAG2 protein, wherein the monoclonal antibody thereby binds to plasma cells which express the JAG2 protein on the surface.

27. The monoclonal antibody of claim 26, which has been raised against the peptide of SEQ ID NO:

3.