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

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

Author Lucena-Araujo, Antonio R. Google Scholar
Kim, Haesook T. Google Scholar
Jacomo, Rafael H. Google Scholar
Melo, Raul A. Google Scholar
Bittencourt, Rosane Google Scholar
Pasquini, Ricardo Google Scholar
Pagnano, Katia Google Scholar
Fagundes, Evandro M. Google Scholar
Chauffaille, Maria de Lourdes Autor UNIFESP Google Scholar
Chiattone, Carlos S. Google Scholar
Lima, Ana S. Google Scholar
Kwaan, Hau C. Google Scholar
Gallagher, Robert Google Scholar
Niemeyer, Charlotte M. Google Scholar
Schrier, Stanley L. Google Scholar
Tallman, Martin S. Google Scholar
Grimwade, David Google Scholar
Ganser, Arnold Google Scholar
Berliner, Nancy Google Scholar
Ribeiro, Raul C. Google Scholar
Lo-Coco, Francesco Google Scholar
Lowenberg, Bob Google Scholar
Sanz, Miguel A. Google Scholar
Rego, Eduardo M. Google Scholar
Institution Universidade de São Paulo (USP)
Dana Farber Canc Inst
Fundacao HEMOPE
Univ Fed Rio Grande do Sul
Univ Fed Parana
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Santa Casa Med Sch
Northwestern Univ
Albert Einstein Canc Ctr
Univ Med Ctr
Stanford Univ
Mem Sloan Kettering Canc Ctr
Kings Coll London
Hannover Med Sch
Harvard Univ
St Jude Childrens Res Hosp
Univ Roma Tor Vergata
Santa Lucia Fdn
Erasmus MC
Valencia Univ Med Sch
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.
Keywords acute promyelocytic leukaemia
International Consortium on Acute Promyelocytic Leukaemia
KMT2E (MLL5)
developing countries
all-trans retinoic acid
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2013/08135-2
CNPq: 573754/2008-0
FAPESP: 2007/55067-1
Date 2014-08-01
Published in British Journal of Haematology. Hoboken: Wiley-Blackwell, v. 166, n. 4, p. 540-549, 2014.
ISSN 0007-1048 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 540-549
Origin http://dx.doi.org/10.1111/bjh.12921
Access rights Closed access
Type Article
Web of Science ID WOS:000340237900009
URI http://repositorio.unifesp.br/handle/11600/38063

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