Baalc expression as a diagnostic marker for acute leukemia

Abstract

Overexpression of the gene, BAALC, in biological samples from a patient is prognostic for tumor aggressiveness and unfavorable patient outcome. The present invention provides polynucleotide primers and probes for assaying for overexpression of BAALC transcripts. Kits containing the primers and probes are also provided. Also provided are antibodies for assaying for overexpression of BAALC proteins as well as peptide immunogens for producing the anti-BAALC antibodies. The present invention also provides methods for characterizing acute myelogenous leukemia, chronic myelogenous leukemia and prostate cancer in a patient, base on detection of BAALC overexpression.

1 . A kit for characterizing acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), or prostate cancer in a patient, said kit comprising:
 a primer set comprising a forward primer comprising a sequence that is identical to a first region in a BAALC transcript and a reverse primer comprising a sequence that is the reverse complement of a second region in a BAALC transcript, wherein said forward primer and said reverse primer are each from 10 to 50 nucleotides in length.   
     
     
         2 . The kit of  claim 1  wherein the primers are selected from the group consisting of
 i) a forward primer having a sequence that is identical to a sequence in the sense strand of exon 6 of the BAALC gene and a reverse primer having a sequence that is complementary to a sequence in the sense strand of exon 8 of the BAALC gene, 
 ii) a forward primer having a sequence that is identical to a sequence in the sense strand of exon 8 of the BAALC gene and a reverse primer that is complementary to a sequence in the sense strand of exon 8 of the BAALC gene, and 
 iii) a forward primer having a sequence that is identical to a sequence in the sense strand of exon 1 of the BAALC gene and a reverse primer that is complementary to a sequence in the sense strand of exon 1 of the BAALC gene. 
 
     
     
         3 . The kit of  claim 1  wherein said primer set is selected from the group consisting of
 i) a forward primer whose sequence comprises SEQ ID NO: 26 and a reverse primer whose sequence comprises SEQ ID NO: 23; 
 ii) a forward primer whose sequence comprises SEQ ID NO: 27 and a reverse primer whose sequence comprises SEQ ID NO: 23; and 
 iii) a forward primer whose sequence comprises SEQ ID NO: 28 and a reverse primer whose sequence comprises SEQ ID NO: 29. 
 
     
     
         4 . The kit of  claim 1  further comprising a probe comprising a sequence that is complementary to the sequence of one strand of the PCR product, wherein a reporter dye is attached to one end of the probe and a quencher dye is attached to another end of the probe. 
     
     
         5 . A polynucleotide probe for characterizing AML, CML or prostate cancer in a patient, wherein said probe comprises a sequence that is complementary to a sequence in exon 1, exon 6, exon 8, or a sequence that spans the exon 6 and exon 8 splice site of a BAALC transcript. 
     
     
         6 . The polynucleotide probe of  claim 5  wherein said probe is from about 20 to about 30 nucleotides in length and comprises a reporter dye on one end thereof and a quenching dye on another end thereof. 
     
     
         7 . An isolated polynucleotide comprising a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and combinations thereof. 
     
     
         8 . The isolated polynucleotide of  claim 7  wherein said polynucleotide encodes a polypeptide comprising a sequence selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22. 
     
     
         9 . The isolated polynucleotide of  claim 7  wherein said polynucleotide is an a transcript of the BAALC gene and comprises a sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16. 
     
     
         10 . An antibody that is immunospecific for one or more polypeptides that are encoded by a transcript of the BAALC gene. 
     
     
         11 . The antibody of  claim 10  wherein one of said one or more polypeptides comprises an amino acid sequence as set forth in SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, or SEQ ID NO: 22. 
     
     
         12 . The antibody of  claim 10  wherein the antibody is prepared by a process which employs an immunogen having a sequence which comprises SEQ ID NO: 35, SEQ ID NO: 36, or SEQ ID NO: 37.