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

Research output: Contribution to journalArticle

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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
Pages (from-to)540-549
Number of pages10
JournalBritish Journal of Haematology
Volume166
Issue number4
DOIs
Publication statusPublished - 2014

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Acute Promyelocytic Leukemia
Anthracyclines
Tretinoin
Confidence Intervals
Drug Therapy
Disease-Free Survival
Survival
Odds Ratio
Hematopoiesis
Clinical Protocols
Genes
Multivariate Analysis
Survival Rate
Recurrence
Incidence

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

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. / 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.

In: British Journal of Haematology, Vol. 166, No. 4, 2014, p. 540-549.

Research output: Contribution to journalArticle

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, Löwenberg, B, Sanz, MA & Rego, EM 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, vol. 166, no. 4, pp. 540-549. https://doi.org/10.1111/bjh.12921
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. / 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. In: British Journal of Haematology. 2014 ; Vol. 166, No. 4. pp. 540-549.
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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.",
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T1 - Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy

T2 - An International Consortium on Acute Promyelocytic Leukaemia study

AU - Lucena-Araujo, Antonio R.

AU - Kim, Haesook T.

AU - Jacomo, Rafael H.

AU - Melo, Raul A.

AU - Bittencourt, Rosane

AU - Pasquini, Ricardo

AU - Pagnano, Katia

AU - Fagundes, Evandro M.

AU - de Lourdes Chauffaille, Maria

AU - Chiattone, Carlos S.

AU - Lima, Ana S.

AU - Kwaan, Hau C.

AU - Gallagher, Robert

AU - Niemeyer, Charlotte M.

AU - Schrier, Stanley L.

AU - Tallman, Martin S.

AU - Grimwade, David

AU - Ganser, Arnold

AU - Berliner, Nancy

AU - Ribeiro, Raul C.

AU - Lo-Coco, Francesco

AU - Löwenberg, Bob

AU - Sanz, Miguel A.

AU - Rego, Eduardo M.

PY - 2014

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N2 - 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.

AB - 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.

KW - Acute promyelocytic leukaemia

KW - All-trans retinoic acid

KW - Developing countries

KW - International Consortium on Acute Promyelocytic Leukaemia

KW - KMT2E (MLL5)

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