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

Antonio R. Lucena-Araujo, Haesook T. Kim, Rafael H. Jacomo, Raul A. Melo, Rosane Bittencourt, Ricardo Pasquini, Katia Pagnano, Evandro M. Fagundes, Maria de Lourdes Chauffaille, Carlos S. Chiattone, Ana S. Lima, Hau C. Kwaan, Robert Gallagher, Charlotte M. Niemeyer, Stanley L. Schrier, Martin S. Tallman, David Grimwade, Arnold Ganser, Nancy Berliner, Raul C. RibeiroFrancesco Lo-Coco, Bob Löwenberg, Miguel A. Sanz, Eduardo M. Rego*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)540-549
Number of pages10
JournalBritish Journal of Haematology
Volume166
Issue number4
DOIs
StatePublished - Aug 2014

Keywords

  • Acute promyelocytic leukaemia
  • All-trans retinoic acid
  • Developing countries
  • International Consortium on Acute Promyelocytic Leukaemia
  • KMT2E (MLL5)

ASJC Scopus subject areas

  • Hematology

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