TY - JOUR
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 - 2014/8
Y1 - 2014/8
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)
UR - http://www.scopus.com/inward/record.url?scp=84904906976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904906976&partnerID=8YFLogxK
U2 - 10.1111/bjh.12921
DO - 10.1111/bjh.12921
M3 - Article
C2 - 24796963
AN - SCOPUS:84904906976
SN - 0007-1048
VL - 166
SP - 540
EP - 549
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -