Methods of diagnosing myelodysplastic syndrome (mds) or leukemia using nucleic acids or fragments encoding flt3 kinase

Abstract

To provide a nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane and is useful for diagnosis of leukemia; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to a region encoded by the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a nucleic acid capable of specifically binding to the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a method for detection of the nucleic acid encoding a receptor protein kinase; and a kit therefor. A nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to the portion of the polypeptide; a nucleic acid capable of specifically binding to the nucleic acid; a method for detection of the nucleic acid; and a kit for detection.

1 . A method of determining the prognosis of a patient diagnosed with myelodysplastic syndrome (MDS) or leukemia, comprising:
 obtaining a sample from the patient;   transmitting the sample for analysis;   receiving information on the presence or absence of a mutation within a region of polynucleotide encoding FLT3 kinase, wherein the region is bounded by SEQ ID NO: 26 and SEQ ID NO: 33; and   correlating the presence of said mutation with a pathological judgment of MDS or acute myeloid leukemia (AML).   
     
     
         2 . The method of  claim 1 , wherein the presence or absence of the mutation is ascertained within a region bounded by SEQ ID NO: 26 and SEQ ID NO: 27. 
     
     
         3 . The method of  claim 1 , wherein the mutation comprises a tandem duplication within a region bounded by SEQ ID NO: 26 and SEQ ID NO: 27. 
     
     
         4 . The method of  claim 1 , wherein the mutation comprises one or more nucleotide insertions. 
     
     
         5 . The method of  claim 1 , further comprising sub-classifying AML as M2, M4, or M5 based on the French-American-British (FAB) classification system. 
     
     
         6 . The method of  claim 1 , wherein the patient is in remission of MDS or leukemia. 
     
     
         7 . The method of  claim 1 , wherein the sample is a nucleic acid sample selected from the group consisting of genomic DNA, cDNA, or mRNA. 
     
     
         8 . The method of  claim 1 , wherein the patient has been diagnosed with MDS. 
     
     
         9 . The method of  claim 1 , wherein the patient has been diagnosed with AML. 
     
     
         10 . The method of  claim 7 , wherein the sample is obtained from myelocytes. 
     
     
         11 . The method of  claim 2 , wherein the mutation comprises one or more nucleotide insertions. 
     
     
         12 . The method of  claim 2  further comprising sub-classifying AML as M2, M4, or M5 based on the French-American-British (FAB) classification system. 
     
     
         13 . The method of  claim 2 , wherein the patient is in remission of MDS or leukemia. 
     
     
         14 . The method of  claim 2 , wherein the sample is a nucleic acid sample selected from the group consisting of genomic DNA, cDNA, or mRNA. 
     
     
         15 . A method of diagnosing or making a prognostic assessment of myelodysplastic syndrome (MDS) or leukemia in a human subject, comprising:
 providing a biological sample from the subject, wherein said sample comprises a nucleic acid which encodes a polypeptide having FLT3 kinase activity;   receiving information on the presence or absence of length mutations in a region of FLT3 of the sample, wherein the region of FLT3 is bounded by SEQ ID NO: 26 and SEQ ID NO: 33; and   correlating the presence of said length mutation with a diagnostic or prognostic assessment of myelodysplastic syndrome (MDS) or leukemia.   
     
     
         16 . The method of  claim 15 , wherein the presence or absence of the length mutation is ascertained within a region bounded by SEQ ID NO: 26 and SEQ ID NO: 27. 
     
     
         17 . The method of  claim 15 , wherein the leukemia is acute myeloid leukemia (AML). 
     
     
         18 . The method of  claim 17 , further comprising sub-classifying AML as M2, M4, or M5 based on the French-American-British (FAB) classification system. 
     
     
         19 . The method of  claim 15 , wherein the presence of said length mutation is indicated in a report of the results of a nucleic acid amplification reaction. 
     
     
         20 . The method of  claim 15 , wherein the information received comprises FLT3 nucleotide sequence. 
     
     
         21 . The method of  claim 20 , wherein the information received comprises FLT3 nucleotide sequence from a region bounded by SEQ ID NO: 26 and SEQ ID NO: 33 or a portion thereof. 
     
     
         22 . The method of  claim 20 , wherein the information received comprises FLT3 nucleotide sequence from a region bounded by SEQ ID NO: 26 and SEQ ID NO: 27 or a portion thereof. 
     
     
         23 . A method for monitoring treatment of myelodysplastic syndrome (MDS) or leukemia characterized by length mutations in a region of FLT3 kinase corresponding to a region bounded by SEQ ID NO: 26 and SEQ ID NO: 33, comprising:
 providing a biological sample from a human subject previously diagnosed as having a length mutation in a region of FLT3 bounded by SEQ ID NO: 26 and SEQ ID NO: 33;   receiving information on the presence or absence of length mutations in the region of FLT3 kinase corresponding to a region bounded by SEQ ID NO: 26 and SEQ ID NO: 33 in polynucleotide from the sample; and   correlating absence of said length mutation in the sample with remission of myelodysplastic syndrome (MDS) or leukemia.   
     
     
         24 . The method of  claim 23 , wherein the nucleic acid sample is genomic DNA. 
     
     
         25 . The method of  claim 24 , wherein the genomic DNA is obtained from one or more myelocytes. 
     
     
         26 . The method of  claim 23 , wherein the subject is in symptomatic remission of MDS or leukemia, and wherein presence of the length mutation is correlated with likelihood of relapse. 
     
     
         27 . A method for determining treatment of leukemia characterized by length mutations in a region of FLT3 kinase bounded by SEQ ID NO: 26 and SEQ ID NO: 27, comprising:
 providing a biological sample from a human subject previously diagnosed as having a length mutation in the region of FLT3 while the subject is in remission;   receiving information on the presence or absence of length mutations in the region in polynucleotide in the sample;   correlating the presence of said length mutation in the sample with likelihood of relapse; and   treating the patient based on said likelihood.   
     
     
         28 . The method of  claim 27 , wherein the nucleic acid sample is genomic DNA. 
     
     
         29 . The method of  claim 28 , wherein the genomic DNA is obtained from one or more myelocytes.