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 for screening a human subject for treatment with a compound that suppresses proliferation of hematopoietic cells expressing a nucleic acid encoding a tandem duplication mutant polypeptide of FLT3 kinase, comprising:
 ascertaining the presence or absence of at least one tandem duplication in the subject in a region of the FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO: 33; and   selecting the human subject based on the presence or absence of the tandem duplication for treatment with said compound.   
     
     
         2 . The method of  claim 1 , wherein the region is defined by SEQ ID NO: 26 and SEQ ID NO: 27. 
     
     
         3 . The method of  claim 1 , wherein the ascertaining step comprises amplifying a portion of a nucleic acid encoding a polypeptide having FLT3 kinase activity from a sample obtained from the patient, thereby generating an amplicon. 
     
     
         4 . The method of  claim 3 , wherein the amplicon comprises polynucleotide from a region of the FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO: 33 or a portion thereof. 
     
     
         5 . The method of  claim 3 , wherein the amplicon comprises polynucleotide from a region of the FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO: 27 or a portion thereof. 
     
     
         6 . The method of  claim 3 , wherein an increase in the length of the amplicon indicates the presence of at least one tandem duplication and/or nucleotide insertion. 
     
     
         7 . A method for drug selection for treatment of hematopoietic stem cell disease, comprising:
 ascertaining whether hematopoietic stem cells from a patient contain a tandem duplication mutation in a region of a FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO:  33; and      selecting a drug based on the presence or absence of the mutation.   
     
     
         8 . The method of  claim 7 , wherein the ascertaining step comprises amplifying a portion of a nucleic acid encoding a polypeptide having FLT3 kinase activity from a sample obtained from the patient, thereby generating an amplicon. 
     
     
         9 . The method of  claim 8 , wherein the amplicon comprises polynucleotide from a region of the FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO: 33 or a portion thereof. 
     
     
         10 . The method of  claim 8 , wherein the amplicon comprises polynucleotide from a region of the FLT3 gene defined by SEQ ID NO: 26 and SEQ ID NO: 27 or a portion thereof. 
     
     
         11 . The method of  claim 8 , wherein an increase in the length of the amplicon indicates the presence of at least one tandem duplication and/or nucleotide insertion. 
     
     
         12 . The method of  claim 7  wherein the hematopoietic stem cell disease is myelodysplastic syndrome (MDS) or leukemia. 
     
     
         13 . The method of  claim 12  wherein the leukemia is acute myeloid leukemia (AML). 
     
     
         14 . The method of  claim 7  wherein the drug regulates proliferation, immune response or signal information transmission of a blood cell or a hematopoietic stem cell.