The present invention encompasses methods for generating mutant j anus kinase 2 (JAK-2), mutant calreticulin (CALR), or thrombopoietin receptor (MPL) modified megakaryocytes (modified MKs) expressing a mutant Janus kinase 2 peptide, a mutant calreticulin peptide, and/or a mutant thrombopoietin receptor peptide, JAK2-, CALR-, and/or MPL-modified platelets as a composition of matter, and methods for using the generated JAK2-, CALR-, and/or MPL- modified platelets.