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. (3rd May 2014)

• Record Type: Journal Article
• Authors: Lucena‐Araujo, Antonio R.; Kim, Haesook T.; Jacomo, Rafael H.; Melo, Raul A.; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M.; de Lourdes Chauffaille, Maria; Chiattone, Carlos S.; Lima, Ana S.; Kwaan, Hau C.; Gallagher, Robert; Niemeyer, Charlotte M.; Schrier, Stanley L.; Tallman, Martin S.; Grimwade, David; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C.; Lo‐Coco, Francesco; Löwenberg, Bob; Sanz, Miguel A.; Rego, Eduardo M.
• Is Part Of: British journal of haematology. Volume 166:Number 4(2014:Aug.)
• Page Start: 540
• Page End: 549
• Publication Date: 2014-05-03
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12921
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12921-abs-0001"> <title>Summary</title> <p>The <italic>KMT2E</italic> (<italic>MLL5</italic>) 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 <italic>KMT2E</italic> might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of <italic>KMT2E</italic> expression on the prognosis of 121 APL patients treated with ATRA and anthracycline‐based chemotherapy. Univariate analysis showed that complete remission (<italic>P </italic>=<italic> </italic>0·006), 2‐year overall survival (OS) (<italic>P </italic>=<italic> </italic>0·005) and 2‐year disease‐free survival (DFS) rates (<italic>P </italic>=<italic> </italic>0·037) were significantly lower in patients with low <italic>KMT2E</italic> expression; additionally, the 2‐year cumulative incidence of relapse was higher in patients with low <italic>KMT2E</italic> expression (<italic>P </italic>=<italic> </italic>0·04). Multivariate analysis revealed that low <italic>KMT2E</italic> expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71–30·1; <italic>P </italic>=<italic> </italic>0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08–0·87; <italic>P </italic>=<italic> </italic>0·029). Evaluated as a continuous variable, <italic>KMT2E</italic> expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49–43·2; <italic>P </italic>=<italic> </italic>0·001) and shorter survival (HR: 0·17, 95% IC: 0·05–0·53; <italic>P </italic>=<italic> </italic>0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99–1·02; <italic>P </italic>=<italic> </italic>0·06). In summary, low <italic>KMT2E</italic> expression may predict poor outcome in APL patients.</p> </abstract>