Targeting the adnexal epithelium: an unusual case of syringometaplasia in a patient on vemurafenib.

Cutaneous adverse events (cAEs) are reported in 90% of all patients on selective BRAF inhibitors and contribute significantly to patient morbidity. Two weeks after initiating vemurafenib for metastatic melanoma, our patient developed a pruritic eruption with numerous, 1-2 mm pink hyperkeratotic follicular papules over his trunk and upper extremities. A biopsy demonstrated squamous metaplasia of the eccrine ducts with irregular hyperplasia of hair follicles sparing the interfollicular epidermis.

Analysis of dermatologic events in vemurafenib-treated patients with melanoma.

Background: Vemurafenib has been approved for the treatment of patients with advanced BRAF(V600E)-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC).

Methods: Dermatologic AEs were assessed from three ongoing trials of BRAF(V600E) mutation-positive advanced melanoma.

RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors.

Background: Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors.

Methods: We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed.

Role for MKL1 in megakaryocytic maturation.

Megakaryoblastic leukemia 1 (MKL1), identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, is highly expressed in differentiated muscle cells and promotes muscle differentiation by activating serum response factor (SRF). Here we show that Mkl1 expression is up-regulated during murine megakaryocytic differentiation and that enforced overexpression of MKL1 enhances megakaryocytic differentiation. When the human erythroleukemia (HEL) cell line is induced to differentiate with 12-O-tetradecanoylphorbol 13-acetate, overexpression of MKL1 results in an increased number of megakaryocytes with a concurrent increase in ploidy.