Mpl mutations in jak2 v617f negative patients with myeloproliferative disease

Abstract

The invention provides compositions and methods for diagnosing a patient as having a myeloproliferative disease by identifying mutations in the MPL gene or gene products.

What is claimed is: 
     
         1 . A method of assessing the myeloproliferative disease status of an individual, comprising:
 (a) processing a sample comprising MPL protein from the individual to generate a processed sample; and   (b) evaluating the processed sample for the presence or absence of one or more MPL protein mutations and the wild type MPL protein, wherein said MPL protein mutations are selected from the group consisting of: W515_P518 del/insKT, T496_A497 insATVI, and R525C fs*14;   wherein
 (i) when the sample shows the presence of one or more of said protein mutations and the absence wild type MPL protein is indicative of the individual having a myeloproliferative disease or being predisposed to myeloproliferative disease, 
 (ii) when the sample shows the presence of wild type MPL protein and the presence of one or more of said protein mutations is indicative of the individual as being predisposed to a myeloproliferative disease, or 
 (iii) when the sample shows the absence of each of said protein mutations is indicative of the individual as having no predisposition to a myeloproliferative disease. 
   
     
     
         2 . The method of  claim 1 , wherein said sample is selected from the group consisting of blood, serum, and plasma. 
     
     
         3 . The method of  claim 1 , wherein said myeloproliferative disease is selected from the group consisting of polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). 
     
     
         4 . The method of  claim 1 , wherein evaluating comprises using antibodies against wild type MPL protein and each of the protein mutations. 
     
     
         5 . The method of  claim 1 , wherein evaluating comprises protein sequencing. 
     
     
         6 . The method of  claim 1 , wherein said individual does not have a pathologic mutation in the JAK2 gene. 
     
     
         7 . The method of  claim 1 , wherein said individual does not have a mutation in the JAK2 gene encoding V617F mutation. 
     
     
         8 . A method of identifying an individual with an increased likelihood of having a myeloproliferative disease, comprising:
 (a) obtaining a processed sample comprising MPL protein from a biological sample obtained from the individual; and   (b) evaluating the processed sample for the presence or absence of one or more of W515_P518 del/insKT, T496_A497 insATVI, and R525C fs*14 mutations;   wherein when one of said mutations is present is indicative of the individual as having an increased likelihood of having a myeloproliferative disease.   
     
     
         9 . The method of  claim 8 , wherein said biological sample is selected from the group consisting of blood, serum, and plasma. 
     
     
         10 . The method of  claim 8 , wherein said myeloproliferative disease is selected from the group consisting of polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). 
     
     
         11 . The method of  claim 8 , wherein evaluating uses antibodies against wild type MPL protein and each of the protein mutations. 
     
     
         12 . The method of  claim 8 , wherein evaluating comprises protein sequencing. 
     
     
         13 . The method of  claim 8 , wherein said individual does not have a pathologic mutation in the JAK2 gene. 
     
     
         14 . The method of  claim 8 , wherein said individual does not have a mutation in the JAK2 gene encoding V617F mutation.