Methods and kits for diagnosing and treating b-cell chronic lymphocytic leukemia

Abstract

The present invention relates to methods and kits for detecting several polynucleotide sequence found to be indicative of a poor prognosis of B-CLL. All the polynucleotides are transcribed from a region on human chromosome 12p21-22. Most of the polynucleotides do not encode larger polypeptides, but may encode small peptides, they may function as RNAs. Four polynucleotides encode a novel protein, which in one preferred embodiment can be used as a cytokine, preferably as an interleukin. Furthermore the invention relates to methods and compositions for treating B-CLL in particular poor prognosis B-CLL.

1 - 41 . (canceled) 
     
     
         42 . A nucleotide sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17 and SEQ ID NO: 18 for use as a medicament. 
     
     
         43 . A transcriptional product selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 for use as a medicament. 
     
     
         44 . An amino acid sequence selected from the group consisting of:
 i) an amino acid sequence of SEQ ID NO: 3,   ii) an amino acid sequence having at least 60% sequence identity compared to the full length sequence of SEQ ID NO: 3   iii) a fragment of SEQ ID NO: 3 having at least 60% sequence identity compared to the full length sequence of SEQ ID NO: 3 for use in a diagnostic method for a subtype of B-CLL having a poor prognosis.   
     
     
         45 . An amino acid sequence according to  claim 44 , said amino acid sequence being a polypeptide having interleukin or cytokine activity. 
     
     
         46 . The amino acid sequence according to any one of  claims 44  or  45 , which folds as a 4-helical cytokine. 
     
     
         47 . Use of an amino acid sequence as defined in any one of  claims 44 - 46  for the preparation of a medicament for the treatment of cancer. 
     
     
         48 . Use according to  claim 47 , wherein the cancer is B-CLL. 
     
     
         49 . A method of immunisation of a patient in need thereof against B-CLL, wherein said immunisation generates an immune response in said patient which recognises a translational product of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11. 
     
     
         50 . A method for producing an antibody with specificity against an isolated polypeptide selected from
 i) an amino acid sequence of SEQ ID NO: 3,   ii) an amino acid sequence having at least 60% sequence identity with the full length SEQ ID   NO: 3,   iii) a fragment of SEQ ID NO: 3 having at least 60% sequence identity compared to full length SEQ ID NO: 3.   
     
     
         51 . The method of  claim 50  wherein said isolated polypeptide has interleukin or cytokine activity. 
     
     
         52 . The method of  claim 50  wherein the isolated polypeptide folds as a 4-helical cytokine. 
     
     
         53 . An antibody obtainable by the method of  claim 50 . 
     
     
         54 . An antibody with specificity against an isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 i) an amino acid sequence of SEQ ID NO: 3,   ii) an amino acid sequence having at least 60% sequence identity compared to the full length sequence of SEQ ID NO:3   iii) a fragment of SEQ ID NO:3 having at least 60% sequence identity compared to the full length sequence of SEQ ID NO:3.