Nucleophosmin protein (npm) mutants, corresponding gene sequences and uses thereof

Abstract

The invention relates to new nucleophosmin protein (NPM) mutants, corresponding gene sequences and relative uses thereof for diagnosis, monitoring of minimal residual disease, prognostic evaluation and therapy of acute myeloid leukaemia (AML).

What is claimed is: 
     
         1 . A method comprising
 detecting, in a sample of nucleic acids, a nucleic acid that encodes one or more mutations in exon 12 of an NPM gene, wherein the nucleic acid comprises an exon 12 sequence coding for position 290 of human nucleophosmin protein (NPM) that results in a loss of a tryptophan residue at position 290,   wherein the detecting comprises identifying the nucleic acid using   (a) oligonucleotide primers in a polymerase chain reaction assay that amplifies the nucleic acid but does not substantially amplify a nucleic acid encoding a wild-type NPM, and/or   (b) an oligonucleotide probe that binds to a nucleic acid encoding the one or more mutations but not to a wild-type NPM.   
     
     
         2 . The method of  claim 1 , wherein the sample is human blood. 
     
     
         3 . The method of  claim 1 , wherein the nucleic acids are in cells. 
     
     
         4 . The method of  claim 1 , wherein both oligonucleotide primers and an oligonucleotide probe are used to identify the nucleic acid. 
     
     
         5 . The method of  claim 4 , wherein the oligonucleotide probe is a hydrolysis probe. 
     
     
         6 . The method of  claim 1 , wherein the detecting comprises real-time PCR. 
     
     
         7 . The oligonucleotide primers used in the method of  claim 1 . 
     
     
         8 . The hydrolysis probe used in the method of  claim 1 . 
     
     
         9 . A kit comprising the oligonucleotide primers and/or the oligonucleotide probe of  claim 1 . 
     
     
         10 . A method comprising
 detecting, in a sample of nucleic acids, a nucleic acid that encodes one or more mutations in exon 12 of an NPM gene, wherein the nucleic acid encodes a signal motif of nuclear export (NES) in the C-terminal region of the NPM gene,   wherein said detecting comprises identifying the nucleic acid using   (a) oligonucleotide primers in a polymerase chain reaction assay that amplifies a nucleic acid encoding the one or more mutations but does not substantially amplify a nucleic acid encoding a wild-type NPM, and/or   (b) an oligonucleotide probe that binds, in a hybridization assay, to a nucleic acid encoding the one or more mutations but not to a wild-type NPM.   
     
     
         11 . The method of  claim 10 , wherein the nucleic acid encoding the one or more mutations further comprises an exon 12 sequence coding for position 290 of human nucleophosmin protein (NPM) that results in a loss of a tryptophan residue at position 290. 
     
     
         12 . The method of  claim 10 , wherein the NES comprises an amino acid sequence LxxxVxxVxL (SEQ ID NO:1), wherein x can be any amino acid. 
     
     
         13 . The method of  claim 10 , wherein the sample is human blood. 
     
     
         14 . The method of  claim 10 , wherein the nucleic acids are in cells. 
     
     
         15 . The method of  claim 10 , wherein both oligonucleotide primers and an oligonucleotide probe are used to identify the nucleic acid. 
     
     
         16 . The method of  claim 15 , wherein the oligonucleotide probe is a hydrolysis probe. 
     
     
         17 . The method of  claim 10 , wherein the detecting comprises real-time PCR. 
     
     
         18 . The oligonucleotide primers used in the method of  claim 10 . 
     
     
         19 . The hydrolysis probe used in the method of  claim 10 . 
     
     
         20 . A kit comprising the oligonucleotide primers and/or the oligonucleotide probe of  claim 10 .