Method of judging leukemia, pre-leukemia or aleukemic malignant blood disease and diagnostic therefor

• US 7,479,371 B2
• Filed: 04/09/2003
• Issued: 01/20/2009
• Est. Priority Date: 04/09/2002
• Status: Expired due to Fees

• Current Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited), Kyowa Medex Co., Ltd. (Resonac Holdings Corp.), The University of Tokyo
• Original Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited), Kyowa Medex Co., Ltd. (Resonac Holdings Corp.), The University of Tokyo
• Inventors: Ando, Kiyoshi, Kohno, Hiroaki, Hotta, Tomomitsu, Ito, Chie, Sato, Hidenao, Furuya, Akiko, Shitara, Kenya, Sugimoto, Seiji
• Primary Examiner(s): Belyavskyi; Michail A
• Application Number:
  US10/510,627
• Publication Number:
  US 20060084122A1
• Time in Patent Office: 2,113 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: G01N 2333/475 Assays involving growth factors
• CPC Class Codes: G01N 33/57426 leukemia

Abstract

The present invention relates to a method for diagnosing leukemia, pre-leukemia or aleukemic malignant blood diseases, a method of discriminating leukemia from pre-leukemia or aleukemic malignant blood diseases, a method of discriminating aplastic anemia from myelodysplastic syndrome, a method of diagnosing delayed engraftment of the hematopoietic stem cells after transplantation of the hematopoietic stem cells, and a method of diagnosing the graft versus host disease, each of said methods comprising quantifying stem cell growth factor (SCGF). The present invention also makes it possible to provide an agent for diagnosing leukemia, pre-leukemia or aleukemic malignant blood diseases and an agent for diagnosing delayed engraftment of the hematopoietic stem cells after transplantation of the hematopoietic stem cells or an agent for diagnosing graft versus host disease (GVHD), each containing as an active ingredient an antibody reacting with stem cell growth factor (SCGF).

Claims

1. A method for diagnosing leukemia, pre-leukemia or aleukemic malignant blood diseases wherein stem cell growth factor (SCGF) in an in-vivo sample is quantified, wherein the method comprises:

obtaining an in-vivo patient sample from a patient suspected of having leukemia, pre-leukemia or aleukemic malignant blood disease;

contacting the patient sample with one or more anti-SCGF antibodies;

detecting and/or quantifying SCGF present in the patient sample in an immunological assay;

thereby obtaining a patient sample SCGF value;

comparing the patient sample SCGF value to a SCGF cut-off value;

wherein the SCGF cut-off value is set based on one or more individuals that do not have leukemia, pre-leukemia, or alenkemic malignant blood disease; and

diagnosing leukemia, pre-leukemia or aleukemic malignant blood disease if the patient sample SCGF value is above the SCGF cut-off value;

wherein the leukemia is acute lymphocytic leukemia (ALL), acute mycloid leukemia (AML), or chronic myeloid leukemia (CML), and the pre-leukemia is myelodysplastic syndrome (MDS), and the aleukemic malignant blood disease is non-Hodgkin'"'"'s lymphoma (NHL) or multiple mycloma (MM).

2. The method according to claim 1, wherein the immunological assay is a sandwich assay.

3. The method according to claim 2, wherein two different anti-SCGF antibodies are used in the sandwich assay, wherein the two different anti-SCGF antibodies react with different epitopes of stem cell growth factor (SCGF).

4. The method according to claim 3, wherein the antibodies are selected from polyclonal and monoclonal antibodies.

5. The method according to claim 4, wherein at least one of the antibodies is a monoclonal antibody, and wherein the at least one monoclonal antibody is selected from a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 6-28 of SEQ. ID No. 1, a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 29-59 of SEQ. ID No. 1, and a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 60-302 of SEQ. ID No. 1.

6. The method of claim 1, wherein the SCGF cut-off value is set by

obtaining one or more in-vivo normal samples from one or more individuals that do not have leukemia, pre-leukemia, or aleukemic malignant blood disease;

contacting the one or more normal samples with one or more anti-SCGF antibodies;

detecting and/or quantifying SCGF present in the one or more normal samples in an immunological assay;

thereby obtaining one or more normal sample SCGF values; and

setting the SCGF cut-off value based on the one or more normal sample SCGF values.

7. The method of claim 1, wherein the in-vivo sample is selected from blood, urine, spinal fluid, and puncture fluid.

8. The method of claim 7, wherein the in-vivo sample is blood, and the blood is selected from whole blood, plasma, and serum.

9. The method of claim 1, wherein the SCGF cut-off value is 18.2 ng/ml.

10. The method of claim 1, wherein the SCGF cut-off value is 15.0 ng/ml.

11. The method of claim 1, wherein the SCGF cut-off value is 13.0 ng/ml.

12. The method of claim 5, wherein the at least one monoclonal antibody is a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 6-28 of SEQ. ID No. 1, wherein the monoclonal antibody is KM2142 produced by hybridoma FERM BP-7922.

13. The method of claim 5, wherein the at least one monoclonal antibody is a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 29-59 of SEQ. ID No. 1, wherein the monoclonal antibody is KM2804 produced by hybridoma FERM BP-7923.

14. The method of claim 5, wherein the at least one monoclonal antibody is a monoclonal antibody recognizing the region shown by the amino acid sequence of residues 60-302 of SEQ. ID No. 1, wherein the monoclonal antibody is KM2945 produced by hybridoma FERM BP-7924.