Distribution of MAP2K1 mutations at protein and exon level in PTFL in comparison with other hematological neoplasias. (A) Schematic diagram of MAP2K1 mutations in PTFL,^3,4  Langerhans cell histiocytosis (LCH),^12-14  hairy cell leukemia^10,11  (including HCLv and conventional HCL [HCLc] with IGHV4-34⁺), splenic diffuse red pulp small B-cell lymphoma (SDRPL),¹⁹  splenic marginal zone lymphoma (SMZL),^17,18  CLL,^15,16  according to NGS studies and/or Sanger analysis. Exons are represented by boxes on the body of MEK1 protein and the main protein domains are represented by larger colored boxes. AL, activation loop; DD, docking domain for ERK1 and ERK2; DVD, domain of versatile docking (MAP3K docking domain); NES, nuclear export sequence; NRR, negative regulatory region; PRD: proline-rich domain. (B) Immunohistochemical analysis of pERK in MAP2K1 mutated and wild-type PTFL cases. Note that the variant allelic frequency (VAF, indicated in parentheses) of MAP2K1 mutations by NGS analysis correlates with the amount of pERK-positive cells.