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.

Lucena-Araujo, A.r., Kim, H.t., Jacomo, R.h., Melo, R.a., Bittencourt, R., Pasquini, R., et al. (2014). 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. BRITISH JOURNAL OF HAEMATOLOGY, 166(4), 540-549 [10.1111/bjh.12921].

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

LO COCO, FRANCESCO;
2014

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
International Consortium on Acute Promyelocytic Leukaemia; KMT2E (MLL5); acute promyelocytic leukaemia; all-trans retinoic acid; developing countries; Adolescent; Adult; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; DNA-Binding Proteins; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Treatment Outcome; Tretinoin; Young Adult
Lucena-Araujo, A.r., Kim, H.t., Jacomo, R.h., Melo, R.a., Bittencourt, R., Pasquini, R., et al. (2014). 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. BRITISH JOURNAL OF HAEMATOLOGY, 166(4), 540-549 [10.1111/bjh.12921].
Lucena Araujo, A; Kim, H; Jacomo, R; Melo, R; Bittencourt, R; Pasquini, R; Pagnano, K; Fagundes, E; de Lourdes Chauffaille, M; Chiattone, C; Lima, A; Kwaan, H; Gallagher, R; Niemeyer, C; Schrier, S; Tallman, M; Grimwade, D; Ganser, A; Berliner, N; Ribeiro, R; LO COCO, F; Lowenberg, B; Sanz, M; Rego, E
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/160497
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