SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis

The molecular basis of advanced systemic mastocytosis (SM).

Autori: Martinelli G, Mancini M, De Benedittis C, Rondoni M, Papayannidis C, Manfrini M, Meggendorfer M, Calogero R, Guadagnuolo V, Fontana MC, Bavaro L, Padella A, Zago E, Pagano L, Zanotti R, Scaffidi L, Specchia G, Albano F, Merante S, Elena C, Savini P, Gangemi D, Tosi P, Ciceri F, Poletti G, Riccioni L, Morigi F, Delledonne M, Haferlach T, Cavo M, Valent P, Soverini S.
Leukemia. 2018 Jan;32(1):139-148. Epub 2017 Jun 16.

Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Reduced or no SETD2 protein expression-and consequently, H3K36 trimethylation-was found in all cases and inversely correlated with disease aggressiveness. Bortezomib and AZD1775 alone or in combination with Midostaurin induced apoptosis and reduced clonogenic growth of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

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