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

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Lucena-Araujo, Antonio R. ^{[1, 2]} ; Kim, Haesook T. ^[3] ; Jacomo, Rafael H. ^{[1, 2]} ; Melo, Raul A. ^[4] ; Bittencourt, Rosane ^[5] ; Pasquini, Ricardo ^[6] ; Pagnano, Katia ^[7] ; Fagundes, Evandro M. ^[8] ; Chauffaille, Maria de Lourdes ^[9] ; Chiattone, Carlos S. ^[10] ; Lima, Ana S. ^{[1, 2]} ; Kwaan, Hau C. ^[11] ; Gallagher, Robert ^[12] ; Niemeyer, Charlotte M. ^[13] ; Schrier, Stanley L. ^[14] ; Tallman, Martin S. ^[15] ; Grimwade, David ^[16] ; Ganser, Arnold ^[17] ; Berliner, Nancy ^[18] ; Ribeiro, Raul C. ^[19] ; Lo-Coco, Francesco ^[20] ; Lowenberg, Bob ^{[21, 22]} ; Sanz, Miguel A. ^[23] ; Rego, Eduardo M. ^{[1, 2]}

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^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Cell Based Therapy, BR-14048900 Ribeirao Preto, SP - Brazil

^[3] Dana Farber Canc Inst, Boston, MA 02115 - USA

^[4] Fundacao HEMOPE, Recife, PE - Brazil

^[5] Univ Fed Rio Grande do Sul, Porto Alegre, RS - Brazil

^[6] Univ Fed Parana, BR-80060000 Curitiba, Parana - Brazil

^[7] Univ Estadual Campinas, Campinas, SP - Brazil

^[8] Univ Fed Minas Gerais, Belo Horizonte, MG - Brazil

^[9] Univ Fed Sao Paulo, Sao Paulo - Brazil

^[10] Santa Casa Med Sch, Sao Paulo - Brazil

^[11] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 - USA

^[12] Albert Einstein Canc Ctr, New York, NY - USA

^[13] Univ Med Ctr, Freiburg - Germany

^[14] Stanford Univ, Stanford, CA 94305 - USA

^[15] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10021 - USA

^[16] Kings Coll London, Sch Med, London WC2R 2LS - England

^[17] Hannover Med Sch, Hannover - Germany

^[18] Harvard Univ, Sch Med, Boston, MA - USA

^[19] St Jude Childrens Res Hosp, Memphis, TN 38105 - USA

^[20] Santa Lucia Fdn, Rome - Italy

^[21] Univ Roma Tor Vergata, Dept Biomedicine & Prevent, Rome - Italy

^[22] Erasmus MC, Rotterdam - Netherlands

^[23] Valencia Univ Med Sch, Valencia - Spain

• Tipo de documento: Artigo Científico
• Fonte: British Journal of Haematology; v. 166, n. 4, p. 540-549, AUG 2014.
• Citações Web of Science: 5

Resumo

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. (AU)

• Processo FAPESP: 07/55067-1 - Analise in vivo e in vitro da acao oncogenica da forma delta n do gene p73 na leucemia promielocitica aguda.
• Beneficiário: Antonio Roberto Lucena de Araújo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs