title: 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.
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.
authors.affiliation: Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil; Centre for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Lucena-Araujo
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Rafael H
authors.initials: RH
authors.lastname: Jacomo
authors.forename: Raul A
authors.initials: RA
authors.lastname: Melo
authors.forename: Rosane
authors.initials: R
authors.lastname: Bittencourt
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
authors.forename: Katia
authors.initials: K
authors.lastname: Pagnano
authors.forename: Evandro M
authors.initials: EM
authors.lastname: Fagundes
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes Chauffaille
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Chiattone
authors.forename: Ana S
authors.initials: AS
authors.lastname: Lima
authors.forename: Hau C
authors.initials: HC
authors.lastname: Kwaan
authors.forename: Robert
authors.initials: R
authors.lastname: Gallagher
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Schrier
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: David
authors.initials: D
authors.lastname: Grimwade
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Rego
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D004268:DNA-Binding Proteins; C460660:KMT2E protein, human; D014212:Tretinoin
keywords: International Consortium on Acute Promyelocytic Leukaemia; KMT2E (MLL5); acute promyelocytic leukaemia; all-trans retinoic acid; developing countries