Methods for treating myelodysplastic syndromes and sideroblastic anemias

Abstract

In certain aspects, the present disclosure provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans. In some embodiments, the compositions of the disclosure may be used to treat or prevent sideroblastic anemias and myelodysplastic syndromes or one or more complications associated sideroblastic anemias and myelodysplastic syndromes.

1 - 64 . (canceled) 
     
     
         65 . A method for treating or preventing a bone marrow disorder in a subject, comprising administering to a subject in need thereof an effective amount of an ActRII antagonist, wherein the subject has bone marrow cells that test positive for one or more mutations in a gene selected from the group consisting of: SF3B1, DNMT3A, and TET2. 
     
     
         66 - 174 . (canceled) 
     
     
         175 . The method of  claim 65 , wherein the ActRII antagonist is an anti-GDF11 antibody. 
     
     
         176 . The method of  claim 65 , wherein the ActRII antagonist is an anti-GDF8 antibody. 
     
     
         177 . The method of  claim 65 , wherein the ActRII antagonist is an anti-activin antibody. 
     
     
         178 . The method of  claim 177 , wherein the ActRII antagonist binds to activin A. 
     
     
         179 . The method of  claim 177 , wherein the ActRII antagonist binds to activin B. 
     
     
         180 . The method of  claim 177 , wherein the ActRII antagonist binds to activin A and activin B. 
     
     
         181 . The method of  claim 65 , wherein the ActRII antagonist is a multispecific antibody that further binds to one or more of: GDF11, GDF8, activin A, activin AB, activin C, activin E, BMP7, GDF3, and BMP6. 
     
     
         182 . The method of  claim 65 , wherein the ActRII antagonist is an anti-ActRII antibody. 
     
     
         183 . The method  claim 182 , wherein the anti-ActRII antibody binds to ActRIIA. 
     
     
         184 . The method of  claim 182 , wherein the anti-ActRII antibody binds to ActRIIB. 
     
     
         185 . The method of  claim 182 , wherein the anti-ActRII antibody binds to ActRIIA and ActRIIB. 
     
     
         186 . The method of  claim 182 , wherein the antibody is a chimeric antibody, a humanized antibody, or a human antibody. 
     
     
         187 . The method of  claim 186 , wherein the antibody is a single-chain antibody, an F(ab′) 2  fragment, a single-chain diabody, a tandem single-chain Fv fragment, a tandem single-chain diabody, a or a fusion protein comprising a single-chain diabody and at least a portion of an immunoglobulin heavy-chain constant region. 
     
     
         188 - 195 . (canceled)