Hairy Cell Leukemia (HCL) [C91.4]
OMIM number: 164757 (BRAF)
Dipl.-Ing. (FH) Tanja Hinrichsen
Hairy cell leukemia belongs to the group of B-cell non-Hodgkin lymphomas. It has a low degree of malignancy and is characterized by splenomegaly, progressive pancytopenia and a slow clinical course. It takes its name from the characteristic fine hair like projections of the leukemic B cells. The cells usually infiltrate the bone marrow.
Two forms can be distinguished: classical HCL (90-95%) and HCL variant (HCL-V, 5-10%). The majority of classical HCL cases have a characteristic immunophenotype (CD5-, CD10-, CD11c+, CD20+, CD25+, CD103+, FMC7+), which allows the differentiation of hairy cells from normal B-cells and HCL-V cells.
Approximately 1/3 of HCL cells have an unclear immunophenotype. Due to the fact that the survival rate of classical HCL can be improved by administration of purin nucleoside analogues (Cladribin, Pentostatin), the ability to distinguish classical HCL from HCL-V and other B-cell lymphomas is of considerable clinical relevance.
Using next generation sequencing (NGS), a mutation in exon 15 of the BRAF gene (BRAF-V600E) was identified in almost all patients with classical HCL, which was undetectable in HCL-V patients. Thus, the BRAF-V600E mutation analysis complements the clinical and laboratory hematological differential diagnostic techniques for suspected HCL and enables molecular monitoring under therapy. The BRAF protein has a central role in the RAS/RAF/MEK/ERK signal pathway and is involved in the regulation of cell proliferation and differentiation as well as apoptosis. The V600E substitution leads to a constitutive, ligand-independent activation of the signal pathway and therefore to a growth advantage for mutant cells.