Use of Telomerase Inhibitors for the Treatment of Myeloproliferative Disorders and Myeloproliferative Neoplasms

Abstract

Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.

1 . A method for alleviating at least one symptom associated with myeloproliferative neoplasms or myelodysplastic syndrome in an individual in need thereof, the method comprising: administering a clinically effective amount of a telomerase inhibitor to the individual, wherein administration of the telomerase inhibitor alleviates at least one symptom associated with myeloproliferative neoplasms or myelodysplastic syndrome. 
     
     
         2 . The method of  claim 1  wherein the myeloproliferative neoplasm is selected from the group consisting of Essential Thrombocythemia (ET), Polycythemia vera (PV), ChronicMyelogenous Leukemia (CML), myelofibrosis (MF), chronic neutrophilic leukemia, chronic eosinophilic leukemia and acute myelogenous leukemia (AML). 
     
     
         3 . The method of  claim 2 , wherein the symptom comprises headache, dizziness or lightheadedness, chest pain, weakness, fainting, vision changes, numbness or tingling of extremities, redness, throbbing or burning pain in extremities (erythromelalgia), enlarged spleen, nosebleeds, bruising, bleeding from mouth or gums, bloody stool, or stroke. 
     
     
         4 . The method of  claim 2  wherein the the myeloproliferative neoplasm (MPN) is Essential Thrombocythemia (ET) or Polycythemia vera (PV). 
     
     
         5 . The method of  claim 2  wherein the myeloproliferative neoplasm (MPN) is myelofibrosis (MF). 
     
     
         6 . The method of  claim 2  wherein the myeloproliferative neoplasm (MPN) is acute myelogenous leukemia (AML). 
     
     
         7 . The method of  claim 1  wherein the myelodysplastic syndrome is selected from the group consisting of refractory anemia, refractory anemia with excess blasts, refractory cytopenia with multilineage dysplasia, refractory cytopenia with unilineage dysplasia, and chronic myelomonocytic leukemia (CMML). 
     
     
         8 . The method of  claim 7  wherein the myelodysplastic syndrome (MDS) is chronic myelomonocytic leukemia (CMML). 
     
     
         9 . A method for reducing neoplastic progenitor cell proliferation in an individual diagnosed with or suspected of having a myeloproliferative neoplasm or myelodysplastic syndrome, the method comprising: administering a clinically effective amount of a telomerase inhibitor to the individual, wherein administration of the telomerase inhibitor reduces neoplastic progenitor cell proliferation in the individual. 
     
     
         10 . The method of  claim 9  wherein the myeloproliferative neoplasm is selected from the group consisting of Essential Thrombocythemia (ET), Polycythemia vera (PV), ChronicMyelogenous Leukemia (CML), myelofibrosis (MF), chronic neutrophilic leukemia, chronic eosinophilic leukemia and acute myelogenous leukemia (AML). 
     
     
         11 . The method of  claim 10  wherein the myeloproliferative neoplasm (MPN) is Essential Thrombocythemia (ET) or Polycythemia vera (PV). 
     
     
         12 . The method of  claim 10  wherein the myeloproliferative neoplasm (MPN) is myelofibrosis (MF). 
     
     
         13 . The method of  claim 10  wherein the myeloproliferative neoplasm (MPN) is acute myelogenous leukemia (AML). 
     
     
         14 . The method of  claim 9  wherein the myelodysplastic syndrome is selected from the group consisting of refractory anemia, refractory anemia with excess blasts, refractory cytopenia with multilineage dysplasia, refractory cytopenia with unilineage dysplasia, and chronic myelomonocytic leukemia (CMML). 
     
     
         15 . The method of  claim 11  wherein reduced neoplastic progenitor cell proliferation results in platelet counts of less than about 600×10 3 /μL in the blood of the individual 
     
     
         16 . The method of  claim 9 , wherein the individual is resistant or intolerant to a prior non-telomerase inhibitor-based therapy. 
     
     
         17 . A method for maintaining blood platelet counts of between less than about 400×10 3 /μL in the blood of an individual diagnosed with or suspected of having essential thrombocythemia, the method comprising: administering a clinically effective amount of a telomerase inhibitor to the individual, wherein administration of the telomerase inhibitor maintains blood platelet counts of less than about 400×10 3 /μL in the individual. 
     
     
         18 . The method of  claim 17 , wherein the telomerase inhibitor is administered no more than once every two weeks. 
     
     
         19 .- 41 . (canceled)