Using multiparameter immunophenotyping, functional studies, high-throughput single-cell RNA sequencing (scRNA-seq), targeted single-cell mutational analysis with simultaneous scRNA-seq (TARGET-seq) (Rodriguez-Meira et al., 2019), and single-cell proteomics, we identify potential targets for the inhibition of pathological megakaryocyte differentiation and megakaryocyte-induced fibrosis and validate G6B as a cell surface marker that may enable specific ablation of myelofibrosis cells using immunotherapy. The gene discussed is MPIG6B; the disease is myelofibrosis.