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Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A methylation:Another “double hit” lymphoma with very poor outcome?

Published in 2014 by Fazila Asmar, Christoffer Hother, Gorjan Kulosman, Marianne Bach Treppendahl, Helene Myrtue Nielsen, Ulrik Ralfkiaer, Anja Pedersen, Michael Boe Møller, Elisabeth Ralfkiaer, Peter de Nully Brown, Kirsten Grønbæk
This paper was not found in any repository; the policy of its publisher is unknown or unclear.
This paper was not found in any repository; the policy of its publisher is unknown or unclear.

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Abstract

MiR34A, B and C have been implicated in lymphomagenesis, but information on their role in normal CD19+ B-cells (PBL-B) and de novo diffuse large B-cell lymphoma (DLBCL) is limited. We show that in normal and activated B-cells miR34A-5p plays a dominant role compared to other miR34 family members. Only miR34A-5p is expressed in PBL-B, and significantly induced in activated B-cells and reactive lymph nodes. In PBL-B, the MIR34A and MIR34B/C promoters are unmethylated, but the latter shows enrichment for the H3K4me3/H3K27me3 silencing mark. Nine de novo DLBCL cases (n=150) carry both TP53 mutation and MIR34A methylation ("double hit") and these patients have an exceedingly poor prognosis with a median survival of 9.4 months (P