Hairy cell leukemia: a chronic B-cell lymphoma with unique clinicopathological features and unresolved molecular mechanisms.

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder that is characterized by pancytopenia, splenomegaly, and hepatomegaly, resulting from the organ-specific infiltration of "hairy" leukemic cells. Despite tremendous therapeutic advances with purine analogs and interferon, approximately half of patients with HCL relapse after initial treatment. The discovery of valine-to-glutamic acid mutation at amino acid 600 on B-rapidly accelerated fibrosarcoma [BRAF(V600E)] in HCL, revealed an aberrant MAPK signaling pathway that drives the proliferation and survival of HCL B cells, provides a promising and effective target for treating patients who have developed resistance to myelotoxic and immune-suppressive drugs. More recently, 2 BRAF(V600E)-based HCL mouse models have been developed that could be extremely useful both for functional studies and for testing the activity of new drugs. This review aims to summarize current understanding of key pathogenic mechanisms underlying HCL development and discusses major hurdles that need to be overcome in the context of other BRAF-mutated malignancies.