Methods to Impair Hematologic Cancer Progenitor Cells and Compounds Related Thereto

Abstract

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful for selectively binding to CD123 and impairing progenitor hematologic cancer cells. These compounds may include cytotoxic moieties such as, for example, radioisotopes or chemotherapeutics.

What is claimed is: 
     
         1 . A method of impairing a hematologic cancer progenitor cell comprising contacting said cell with a compound that selectively binds to CD123 in an amount effective to cause impairment of said cell. 
     
     
         2 . The method of  claim 1 , wherein said compound comprises an antibody. 
     
     
         3 . The method of  claim 2 , wherein said compound further comprises a cytotoxic agent. 
     
     
         4 . The method of  claim 3 , wherein said cytotoxic agent is a radioisotope. 
     
     
         5 . The method of  claim 4 , wherein said radioisotope is selected from the group consisting of  211 Astatine and  131 Iodine. 
     
     
         6 . The method of  claim 1 , wherein said impairment is cell death. 
     
     
         7 . The method of  claim 1 , wherein said hematologic cancer is leukemia or malignant lymphoproliferative disorders. 
     
     
         8 . The method according to  claim 7 , wherein said leukemia is selected from the group consisting of acute myelogenous leukemia, chronic myelogenous leukemia, melodysplastic syndrome, acute lymphoid leukemia, chronic lymphoid leukemia, and myelodysplastic syndrome. 
     
     
         9 . The method according to  claim 7 , wherein said malignant lymphoproliferative disorder is lymphoma. 
     
     
         10 . The method according to  claim 9 , wherein said lymphoma is selected from the group consisting of multiple myeloma, non-Hodgkin's lymphoma, Burkitt's lymphoma, and follicular lymphoma (small cell and large cell). 
     
     
         11 . A compound that binds selectively to CD123 and impairs hematologic cancer progenitor cells. 
     
     
         12 . The compound of  claim 11 , wherein said compound comprises an antibody. 
     
     
         13 . The compound of  claim 12 , wherein said compound further comprises a cytotoxic agent. 
     
     
         14 . The compound of  claim 13 , wherein said cytotoxic agent is a radioisotope. 
     
     
         15 . The compound of  claim 14 , wherein said radioisotope is selected from the group consisting of  211 Astatine and  131 Iodine. 
     
     
         16 . An assay for detecting the presence of hematologic cancer progenitor cells in a sample, comprising detecting the presence of CD123 in said sample. 
     
     
         17 . The assay of  claim 16 , wherein the presence of CD123 is detected by introducing a compound that selectively binds to CD123 and determining whether the compound binds to a component of said sample.