Killing two birds with one stone: BRAF V600E inhibitor therapy for hairy cell leukemia and Langerhans/dendritic cell sarcoma

Dear Editor, We read with great interest the article published in Annals of Hematology on a patient with Langerhans/dendritic cell sarcoma arising from hairy cell leukemia with both lesions demonstrating almost identical karyotypes and identical clonal immunoglobulin gene rearrangements [1]. This case is very interesting in light of fresh data on BRAF V600E mutations in several different tumor types [2]. Whole exome sequencing of patients with hairy cell leukemia has revealed BRAF V600E mutation [3]. This BRAFV600E mutation has been described as a diseasedefining event [3] in hairy cell leukemia and has been implicated in the pathogenesis of hairy cell leukemia. Langerhans cell histiocytoses have also been reported to harbor the BRAFV600E mutation [4]. Histiocytoses are extremely rare diseases with variable clinical syndromes and BRAFV600E mutations have been reported in multiple histiocytoses subtypes including Erdheim–Chester disease [5]. In the light of these results, the case reported is very fascinating [1]. It may be interesting to profile the BRAFV600E status of the hairy cell leukemic clone and the histiocytic/dendritic sarcoma clone. If confirmed, this could suggest clonality and may also indicate a common origin of these diverse rare diseases. Moreover, for this particular patient this may have implications for targeted therapy. Vemurafenib, a BRAF inhibitor has been recently Food and Drug Administration approved for the therapy of BRAFV600E mutant metastatic melanoma [6]. Although hairy cell leukemia is a treatable disease with standard regimens, rare relapsed patients could still benefit from BRAF inhibitor targeted therapy and a proof of concept study has already been reported [7]. Some patients with Langerhans cell histocytoses may have an aggressive clinical course and patients with refractory disease may have few options. BRAF inhibitor-targeted therapy may be the way to kill two birds with one stone such as in this patient if BRAFV600E mutation is confirmed.