Mutations in the RAS-BRAF-MAPK-ERK pathway define a specific subgroup of patients with adverse clinical features and provide new therapeutic options in chronic lymphocytic leukemia.
Here we present an unusual case of a patient with TP53-mutated chronic lymphocytic leukemia (CLL) treated with a PI3Kδ inhibitor evolving to clonally related Langerhans cell histiocytosis (LCH) with acquired BRAFV600E and STK11 mutations and loss of expression of PAX-5 and other examined B cell markers.
Mice with B-cell-restricted BRAF<sup>V600E</sup> expression crossed with the Eµ-TCL1 model of chronic lymphocytic leukemia (CLL) developed leukemia significantly earlier (median, 4.9 vs 8.1 months; <i>P</i> < .001) and had significantly shorter lifespan (median, 7.3 vs 12.1 months; <i>P</i> < .001) versus BRAF wild-type counterparts.
BRAF inhibition increased mortality and CLL expansion in mice harboring CLL xenografts; however, SYK or MEK inhibition prevented CLL proliferation and increased animal survival.