Impact of MLL5 expression on decitabine efficacy and DNA methylation in acute myeloid leukemia.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Humphries, R Keith
MetadataShow full item record
AbstractHypomethylating agents are widely used in patients with myelodysplastic syndromes and unfit patients with acute myeloid leukemia. However, it is not well understood why only some patients respond to hypomethylating agents. We found previously that the effect of decitabine on hematopoietic stem cell viability differed between Mll5 wildtype and null cells. We therefore investigated the role of MLL5 expression levels on outcome of acute myeloid leukemia patients who were treated with decitabine. MLL5 above the median expression level predicted longer overall survival independent of DNMT3A mutation status in bivariate analysis (median overall survival for high vs. low MLL5 expression, 292 vs. 167 days, P=.026). In patients who received 3 or more courses decitabine, high MLL5 expression and wildtype DNMT3A independently predicted improved overall survival (median overall survival for high vs. low MLL5 expression, 468 vs. 243 days, P=.012). In transformed murine cells, loss of Mll5 was associated with resistance to low-dose decitabine, less global DNA methylation in promoter regions, and reduced DNA demethylation upon decitabine treatment. Together, these data support our clinical observation of improved outcome in decitabine treated patients who express MLL5 at high levels, and suggest a mechanistic role of MLL5 in the regulation of DNA methylation.
CitationImpact of MLL5 expression on decitabine efficacy and DNA methylation in acute myeloid leukemia. 2014: Haematologica
The following license files are associated with this item:
- DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia.
- Authors: Metzeler KH, Walker A, Geyer S, Garzon R, Klisovic RB, Bloomfield CD, Blum W, Marcucci G
- Issue date: 2012 May
- MLL5 expression as a biomarker for DNA hypermethylation and sensitivity to epigenetic therapy.
- Authors: Milne TA
- Issue date: 2014 Sep
- Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia.
- Authors: Fabiani E, Leone G, Giachelia M, D'alo' F, Greco M, Criscuolo M, Guidi F, Rutella S, Hohaus S, Voso MT
- Issue date: 2010 Dec
- Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials.
- Authors: Yun S, Vincelette ND, Abraham I, Robertson KD, Fernandez-Zapico ME, Patnaik MM
- Issue date: 2016
- A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy.
- Authors: Lübbert M, Rüter BH, Claus R, Schmoor C, Schmid M, Germing U, Kuendgen A, Rethwisch V, Ganser A, Platzbecker U, Galm O, Brugger W, Heil G, Hackanson B, Deschler B, Döhner K, Hagemeijer A, Wijermans PW, Döhner H
- Issue date: 2012 Mar