Figure 1.

Overview of the mitogen-activated protein kinase (MAPK)-driven hematopoietic neoplasms with common molecular alterations but divergent phenotypes. (A) Diagram demonstrating the divergent hematopoietic development of histiocytic neoplasms and hairy cell leukemia. (B) Diagram of the MAPK and PI3K-AKT signaling pathways with description of the activation of the RAS proteins (HRAS, KRAS, and NRAS) with annotation of the signaling proteins affected by genetic alterations in the histiocytic neoplasms, classical hairy cell leukemia, IGHV4-34⁺ classical hairy cell leukemia, and hairy cell leukemia variant. (C) Timeline of the discovery of recurrent BRAF^V600E mutations in the MAPK-driven hematological neoplasms. (D) Timeline of the discovery of recurrent MAP2K1 mutations in the MAPK-driven hematological neoplasms. LCH, Langerhans cell histiocytosis; ECD, Erdheim–Chester disease; JXG/AXG, juvenile xanthogranuloma/adult xanthogranuloma; RDD, Rosai–Dorfman–Destombes disease; ICH, indeterminate cell histiocytosis; cHCL, classical hairy cell leukemia; vHCL, hairy cell leukemia variant; IGHV, immunoglobulin heavy chain variable; HSC, hematopoietic stem cell; MPP, multipotent progenitor; CMP, common myeloid progenitor; GMP, granulocyte–monocyte progenitor; MDP, monocyte–dendritic cell progenitor; CLP, common lymphoid progenitor; Pro-B, pro-B-lymphocyte; RTK, receptor tyrosine kinase.