RGD Reference Report - Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study. - Rat Genome Database

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Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study.

Authors: Lucena-Araujo, AR  Kim, HT  Jacomo, RH  Melo, RA  Bittencourt, R  Pasquini, R  Pagnano, K  Fagundes, EM  De Lourdes Chauffaille, M  Chiattone, CS  Lima, AS  Kwaan, HC  Gallagher, R  Niemeyer, CM  Schrier, SL  Tallman, MS  Grimwade, D  Ganser, A  Berliner, N  Ribeiro, RC  Lo-Coco, F  Lowenberg, B  Sanz, MA  Rego, EM 
Citation: Lucena-Araujo AR, etal., Br J Haematol. 2014 Aug;166(4):540-9. doi: 10.1111/bjh.12921. Epub 2014 May 3.
RGD ID: 9588539
Pubmed: PMID:24796963   (View Abstract at PubMed)
DOI: DOI:10.1111/bjh.12921   (Journal Full-text)

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0.006), 2-year overall survival (OS) (P = 0.005) and 2-year disease-free survival (DFS) rates (P = 0.037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0.04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7.18, 95% confidence interval [CI]: 1.71-30.1; P = 0.007) and shorter OS (hazard ratio [HR]: 0.27, 95% CI: 0.08-0.87; P = 0.029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10.3, 95% CI: 2.49-43.2; P = 0.001) and shorter survival (HR: 0.17, 95% IC: 0.05-0.53; P = 0.002), while the association with DFS was of marginal significance (HR: 1.01; 95% CI: 0.99-1.02; P = 0.06). In summary, low KMT2E expression may predict poor outcome in APL patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute promyelocytic leukemia severityIEP 9588539mRNA:decreased expression:peripheral blood more ...RGD 
acute promyelocytic leukemia severityISOKMT2E (Homo sapiens)9588539; 9588539mRNA:decreased expression:peripheral blood more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kmt2e  (lysine methyltransferase 2E)

Genes (Mus musculus)
Kmt2e  (lysine (K)-specific methyltransferase 2E)

Genes (Homo sapiens)
KMT2E  (lysine methyltransferase 2E (inactive))


Additional Information