Methods for identifying compounds which modulate hematopoiests
The present invention relates to methods for the diagnosis and treatment of hematological disorders. Specifically, the present invention identifies the differential expression of 131, 148, 199, 12303, 13906, 15513, 17822, 302, 5677, 194, 14393, 28059, 7366, 12212, 1981, 261, 12416, 270, 1410, 137, 1871, 13051, 1847, 1849, 15402, 340, 10217, 837, 1761, 8990 and 13249 genes in tissues relating to hematological disorders sensation, relative to their expression in normal, or non-hematological disorders disease states, and/or in response to manipulations relevant to hematological disorders. The present invention describes methods for the diagnostic evaluation and prognosis of various hematological disorders, and for the identification of subjects exhibiting a predisposition to such conditions. The invention also provides methods for identifying a compound capable of modulating hematological disorders. The present invention also provides methods for the identification and therapeutic use of compounds as treatments of hematological disorders.
1. A method for identifying a candidate compound that modulates hematopoiesis, comprising:
i) combining a compound to be tested with hematopoletic cells expressing a polypeptide selected from the group consisting of:
a) a polypeptide comprising the amino acid sequence of SEQ ID NO:26, wherein the polypeptide has chloride channel protein activity; and
b) a polypeptide encoded by the nucleotide sequence set forth in SEQ ID NO:25, wherein the polypeptide has chloride channel protein activity; under conditions suitable for binding of the test compound to the polypeptide;
ii) detecting binding of the test compound to the polypeptide to thereby identify a compound which binds to the polypeptide; and
iii) determining if the hematopoietic cells differentiate into mature cells; thereby identifying a compound that modulates hematopolesis.
2. The method of claim 1 , wherein the compound is selected from the group consisting of a small molecule, a peptide an and antibody.
3. The method of claim 1 , wherein the polypeptide further comprises a heterologous signal sequence.
4. The method of claim 1 , wherein the binding of the test compound to the polypeptide is detected by an assay selected from the group consisting of:
a) a competition binding assay;
b) an immunoassay; and
c) a yeast two-hybrid assay.
5. The method of claim 1 , wherein the binding of the test compound to the polypeptide is detected by assaying for chloride channel activity of the polypeptide.
6. The method of claim 1 , wherein the polypeptide further comprises glutathione-S-transferase.