MAP-Kinase-Driven Hematopoietic Neoplasms: A Decade of Progress in the Molecular Age
- 1Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas 77030, USA
- 2Department of Pediatrics, Division of Pediatric Hematology-Oncology, Baylor College of Medicine, Houston, Texas 77030, USA
- 3Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
- 4Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
- 5Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
- Correspondence: abdelwao{at}mskcc.org, durhamb{at}mskcc.org
Abstract
Mutations in members of the mitogen-activated protein kinase (MAPK) pathway are extensively studied in epithelial malignancies, with BRAF mutations being one of the most common alterations activating this pathway. However, BRAF mutations are overall quite rare in hematological malignancies. Studies over the past decade have identified high-frequency BRAFV600E, MAP2K1, and other kinase alterations in two groups of MAPK-driven hematopoietic neoplasms: hairy cell leukemia (HCL) and the systemic histiocytoses. Despite HCL and histiocytoses sharing common molecular alterations, these are phenotypically distinct malignancies that differ in respect to clinical presentation and suspected cell of origin. The purpose of this review is to highlight the molecular advancements over the last decade in the histiocytic neoplasms and HCL and discuss the impact these insights have had on our understanding of the molecular pathophysiology, cellular origins, and therapy of these enigmatic diseases as well as perspectives for future research directions.
