Sialyltransferase st3gal6 as a marker for multiple myeloma

Abstract

The present invention relates to the sialyltransferase ST3GAL6 for use as a biomarker for multiple myeloma, and especially as a marker for myelomas with inferior survival rates. The inventors have shown that glycosylation gene expression is dysregulated in Multiple Myeloma and that overexpression of the sialyltransferase ST3GAL6 is associated with inferior survival rates in patients.

1 . A method of determining the prognosis of a multiple myeloma patient or diagnosing multiple myeloma in a patient the method comprising the steps of:
 determining the levels or activity of at least one biomarker in a sample obtained from the patient, wherein the biomarker comprises (i) ST3GAL6, (ii) FUCA1, (iii) ST3GAL1, or (iv) a combination thereof, and   comparing the level or activity of the biomarker in the sample with the level or activity of the biomarker in a control sample.   
     
     
         2 . The method as claimed in  claim 1 , wherein the biomarker comprises FUCA1, and wherein a decreased level or activity of FUCA1 in the sample relative to the control sample is predictive of a reduced survival rate or indicates the presence of multiple myeloma in the patient. 
     
     
         3 . The method as claimed in  claim 1 , wherein the biomarker comprises ST3GAL1, and wherein an increased level or activity of ST3GAL1 in the sample relative to the control sample is predictive of a reduced survival rate or indicates the presence of multiple myeloma in the patient. 
     
     
         4 . The method of  claim 1 , wherein the biomarker comprises ST3GAL6, and wherein an increased level or activity of ST3GAL6 in the sample relative to the control sample is predictive of a reduced survival rate or indicates the presence of multiple myeloma in the patient. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . The method as claimed in  claim 1  wherein the diagnosis is of monoclonal gammopathy of undetermined significance. 
     
     
         8 . A method of determining the treatment regimen for a multiple myeloma patient comprising the steps of:
 determining the levels or activity of at least one biomarker in a sample obtained from the patient, wherein the biomarker comprises (i) ST3GAL6, (ii) FUCA1, (iii) ST3GAL1, or (iv) a combination thereof, and   comparing the level or activity of the biomarker in the sample with the level or activity of the biomarker in a control sample.   
     
     
         9 . The method as claimed in  claim 8 , wherein the biomarker comprises FUCA1, and wherein a decreased level or activity of FUCA1 in the sample relative to the control sample indicates treatment with a FUCA1 potentiator would be beneficial to the patient. 
     
     
         10 . The method as claimed in  claim 8 , wherein the biomarker comprises ST3GAL1, and wherein an increased level or activity of ST3GAL1 in the sample relative to the control sample indicates treatment with a ST3GAL1 inhibitor would be beneficial to the patient. 
     
     
         11 . The method as claimed in  claim 1  wherein the sample is a blood, plasma, serum or tissue sample. 
     
     
         12 . The method of  claim 1  wherein the level of the biomarker is determined by immunohistochemistry, immunocytochemistry, RNA/DNA analysis, an ELISA assay, a competitive or inhibition ELISA, a sandwich ELISA assay, a micro-array based assay, a functionalised nanoparticle assay, QDots, F1 tags, electro sensors, a flow cytometry assay or a real-time chip-based assay assays. 
     
     
         13 . The method of  claim 1 , wherein the control sample is from at least one healthy subject. 
     
     
         14 - 22 . (canceled) 
     
     
         23 . A method of reducing or alleviating multiple myeloma in a patient comprising the step of administering a modulator of ST3GAL6 in an amount sufficient to decrease ST3GAL6 expression or activity, a modulator of ST3GAL1 in an amount sufficient to decrease ST3GAL1 expression or activity, and/or a modulator of FUCA1 in an amount sufficient to increase FUCA1 expression or activity. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The method as claimed in  claim 23  wherein the modulator is an interfering RNA specific for ST3GAL6 or ST3GAL1, a ST3GAL6 or ST3GAL1 enzyme inhibitor or a glycosyltransferase inhibitor. 
     
     
         27 . The method as claimed in  claim 23  wherein the modulator is a FUCA1 enzyme potentiator. 
     
     
         28 - 30 . (canceled) 
     
     
         31 . The method of  claim 8 , wherein the biomarker comprises ST3GAL6, and wherein an increased level or activity of ST3GAL6 in the sample relative to the control sample indicates treatment with a ST3GAL6 inhibitor would be beneficial to the patient. 
     
     
         32 . The method of  claim 8 , wherein the sample is a blood, plasma, serum or tissue sample. 
     
     
         33 . The method of  claim 8 , wherein the level of the biomarker is determined by immunohistochemistry, immunocytochemistry, RNA/DNA analysis, an ELISA assay, a competitive or inhibition ELISA, a sandwich ELISA assay, a micro-array based assay, a functionalised nanoparticle assay, QDots, F1 tags, electro sensors, a flow cytometry assay or a real-time chip-based assay. 
     
     
         34 . The method of  claim 8 , wherein the control sample is from at least one healthy subject.