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
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorRafael H. Jacomo
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorRosane Bittencourt
Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorRicardo Pasquini
Federal University of Paraná, Curitiba, Brazil
Search for more papers by this authorEvandro M. Fagundes
Federal University of Minas Gerais, Belo Horizonte, Brazil
Search for more papers by this authorMaria de Lourdes Chauffaille
Federal University of Sao Paulo, Sao Paulo, Brazil
Search for more papers by this authorCarlos S. Chiattone
Santa Casa Medical School, Sao Paulo, Brazil
Search for more papers by this authorAna S. Lima
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorHau C. Kwaan
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Search for more papers by this authorRobert Gallagher
Albert Einstein Cancer Center, New York, NY, USA
Search for more papers by this authorCharlotte M. Niemeyer
University Medical Centre, Freiburg, Germany
Search for more papers by this authorMartin S. Tallman
Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York, NY, USA
Search for more papers by this authorDavid Grimwade
King's College London School of Medicine, London, UK
Search for more papers by this authorRaul C. Ribeiro
St. Jude Children's Research Hospital, Memphis, TN, USA
Search for more papers by this authorFrancesco Lo-Coco
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Santa Lucia Foundation, Rome, Italy
Search for more papers by this authorBob Löwenberg
Erasmus University Medical Centre, Rotterdam, The Netherlands
Search for more papers by this authorMiguel A. Sanz
Valencia University Medical School, Valencia, Spain
Search for more papers by this authorCorresponding Author
Eduardo M. Rego
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Correspondence: Eduardo M. Rego, MD, PhD, Medical School of Ribeirão Preto, University of São Paulo. Av. Bandeirantes, 3900, Ribeirao Preto, SP 14048-900, Brazil.
E-mail: [email protected]
Search for more papers by this authorAntonio R. Lucena-Araujo
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorRafael H. Jacomo
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorRosane Bittencourt
Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorRicardo Pasquini
Federal University of Paraná, Curitiba, Brazil
Search for more papers by this authorEvandro M. Fagundes
Federal University of Minas Gerais, Belo Horizonte, Brazil
Search for more papers by this authorMaria de Lourdes Chauffaille
Federal University of Sao Paulo, Sao Paulo, Brazil
Search for more papers by this authorCarlos S. Chiattone
Santa Casa Medical School, Sao Paulo, Brazil
Search for more papers by this authorAna S. Lima
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorHau C. Kwaan
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Search for more papers by this authorRobert Gallagher
Albert Einstein Cancer Center, New York, NY, USA
Search for more papers by this authorCharlotte M. Niemeyer
University Medical Centre, Freiburg, Germany
Search for more papers by this authorMartin S. Tallman
Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York, NY, USA
Search for more papers by this authorDavid Grimwade
King's College London School of Medicine, London, UK
Search for more papers by this authorRaul C. Ribeiro
St. Jude Children's Research Hospital, Memphis, TN, USA
Search for more papers by this authorFrancesco Lo-Coco
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Santa Lucia Foundation, Rome, Italy
Search for more papers by this authorBob Löwenberg
Erasmus University Medical Centre, Rotterdam, The Netherlands
Search for more papers by this authorMiguel A. Sanz
Valencia University Medical School, Valencia, Spain
Search for more papers by this authorCorresponding Author
Eduardo M. Rego
Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil
Correspondence: Eduardo M. Rego, MD, PhD, Medical School of Ribeirão Preto, University of São Paulo. Av. Bandeirantes, 3900, Ribeirao Preto, SP 14048-900, Brazil.
E-mail: [email protected]
Search for more papers by this authorSummary
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.
Supporting Information
| Filename | Description |
|---|---|
| bjh12921-sup-0001-FigS1-S3-TableS1.docWord document, 2 MB | Data S1. Statistical analysis of the supplementary data. Fig S1. Overall survival in APL patients divided into quartiles (Q) according to KMT2E/ABL1 expression. Fig S2. Receiver operating characteristic (ROC) curve analysis to define the optimal cut-off point for KMT2E expression. Fig S3. Overall survival in APL patients according to age (younger than 50 years vs. older than 50 years). Table SI. Univariable and multivariable Cox analysis for complete remission, overall survival and disease-free survival according to KMT2E transcript levels (categorical variable). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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