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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study

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Autor(es):
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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 Silvia [1, 2] ; Ruiz-Argueelles, Guillermo [11] ; Soledad Undurraga, Maria [12] ; Martinez, Lem [13] ; Kwaan, Hau C. [14] ; Gallagher, Robert [15] ; Niemeyer, Charlotte M. [16] ; Schrier, Stanley L. [17] ; Tallman, Martin S. [18] ; Grimwade, David [19] ; Ganser, Arnold [20] ; Berliner, Nancy [21] ; Ribeiro, Raul C. [22] ; Lo-Coco, Francesco [23, 24] ; Lowenberg, Bob [25] ; Sanz, Miguel A. [26] ; Rego, Eduardo M. [27, 1, 2]
Número total de Autores: 27
Afiliação do(s) autor(es):
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[1] Med Sch Ribeirao Preto, Ribeirao Preto - Brazil
[2] Ctr Cell Based Therapy, Ribeirao Preto - 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] Clin Ruiz Puebla, Puebla - Mexico
[12] Hosp Salvador, Santiago - Chile
[13] Asociac Espanola Primera Socorros Mutuos, Montevideo - Uruguay
[14] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 - USA
[15] Albert Einstein Canc Ctr, New York, NY - USA
[16] Univ Med Ctr, Freiburg - Germany
[17] Stanford Univ, Stanford, CA 94305 - USA
[18] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY - USA
[19] Kings Coll London, Sch Med, London WC2R 2LS - England
[20] Hannover Med Sch, Hannover - Germany
[21] Harvard Univ, Sch Med, Boston, MA - USA
[22] St Jude Childrens Res Hosp, Memphis, TN 38105 - USA
[23] Univ Roma Tor Vergata, Rome - Italy
[24] Santa Lucia Fdn, Rome - Italy
[25] Erasmus Univ, Med Ctr, Rotterdam - Netherlands
[26] Univ Valencia, Sch Med, Valencia - Spain
[27] Univ Sao Paulo, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 27
Tipo de documento: Artigo Científico
Fonte: ANNALS OF HEMATOLOGY; v. 93, n. 12, p. 2001-2010, DEC 2014.
Citações Web of Science: 14
Resumo

Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITDpositive patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITDnegative patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval {[}CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy. (AU)

Processo FAPESP: 98/14247-6 - Center for Research on Cell-Based Therapy
Beneficiário:Marco Antonio Zago
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
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
Linha de fomento: Bolsas no Brasil - Doutorado