PROSER1 is an integral component of TOPD complexes in hematopoietic cells. (A) Bar charts showing Human Protein Atlas normalized mRNA expression (nTPM) across 40 human tissue types for PROSER1, TET2, TET3, PSPC1, OGT, TET1, and TBP (reference). All TOPD mRNA transcripts, except TET1, are highly expressed in BM. (B) Volcano plot showing protein hits from FLAG M2 immunoprecipitation and mass spectrometry (IP-MS) in K562 cells overexpressing FLAG-tagged full-length human TET2 compared to wild-type control (n = 3 biological replicates). Dotted lines indicate fourfold change and P value of .05. TOPD complex partners are highlighted and identified. See supplemental Table 2 for full list of enriched proteins in IP-MS experiment. (C) Western blot of input and 10× concentration eluates from FLAG M2 IP on independent lysates from wild-type K562 or K562 cells overexpressing FLAG-tagged full-length human TET2. Asterisk (∗) indicates a nonspecific reactive band. (D) Same as in panel C but for lysates obtained from the human dendritic cell line, CAL-1, overexpressing FLAG-tagged full-length human TET2. (E) Bar chart showing frequency of all PROSER1 and TET2 mutations found in hematological malignancies and listed in COSMIC³³ and cBioPortal³⁴ databases. (F) Lollipop diagram indicating PROSER1 alterations (missense, truncating, deletion, and splice mutations) identified in human hematopoietic malignancies. The change in amino acid sequence as well as disease subtype is shown. Mutational data were curated from COSMIC³³ and cBioPortal.³⁴ AML, acute myeloid leukemia; B-ALL, B-cell acute lymphoblastic leukemia; DLBCL, diffuse large B-cell lymphoma; FC, fold change; NK, natural killer.